The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The user-specified target is Rattus norvegicus Gsta4, annotated in UniProt as glutathione S-transferase alpha-4 (GST α4; often discussed as the GSTA4-4 isoenzyme in enzymology literature). In the retrieved full-text literature set, the accession-level mapping “P14942 → rat Gsta4” and all UniProt-listed synonyms (e.g., “GST 8-8”, “GST K”, “GST Yk”) were not explicitly stated, so the UniProt accession verification remains database-dependent; however, the functional identity is strongly constrained by consistent descriptions of alpha-class cytosolic GST A4-4 as the enzyme specialized for conjugating lipid peroxidation-derived alkenals such as 4-hydroxynonenal (4-HNE). All mechanistic and biological evidence below is restricted to this GST alpha-4 / GSTA4-4 entity and its orthologous biology. (hayes2005glutathionetransferases. pages 9-12, hayes2005glutathionetransferases. pages 19-21)
Cytosolic GSTs are typically homo- or heterodimeric enzymes with an N-terminal G-site (binds/activates glutathione, GSH) and a C-terminal H-site (binds hydrophobic electrophilic substrates). In alpha-class GSTs (including GSTA4-4), a tyrosine residue participates in GSH activation chemistry; the overall catalytic cycle supports nucleophilic attack by GSH on electrophilic substrates to generate a GSH conjugate suitable for downstream export/metabolism. (lv2023overexpressionofglutathione pages 2-4)
4-HNE is a reactive α,β-unsaturated aldehyde generated during lipid peroxidation under oxidative stress. A major cellular clearance pathway is GSH conjugation (Michael addition) catalyzed predominantly by GSTA4-4. Classic substrate tables in authoritative reviews list GSTA4-4 as acting on 4-HNE and related lipid-derived hydroxyalkenals (e.g., 4-hydroxydecenal). (hayes2005glutathionetransferases. pages 9-12)
The central biochemical reaction is:
GSH + lipid alkenal ⇌ GS-alkenal (e.g., 4-HNE → GS-HNE)
Structural/enzymology work shows GSTA4-4 combines high chemoselectivity for HNE with unusual stereochemical behavior: it accepts both 4R- and 4S-HNE with minimal preference but produces stereoselective glutathionylated products (e.g., 3S-glutathionyl-4-hydroxynonanal), reflecting a pre-organized active site. (balogh2010substratespecificitycombined pages 1-2)
GSTA4-4 is repeatedly characterized as unusually efficient for lipid-derived α,β-unsaturated aldehydes, especially 4-HNE; a comparative metric from structural/kinetic work notes that a related alpha GST (GSTA1-1) has ~50-fold lower kcat/Km for HNE than GSTA4-4, underscoring specialization. (balogh2010substratespecificitycombined pages 1-2)
A major recent mechanistic development is explicit quantification of reversibility in GSTA4-4-catalyzed Michael addition chemistry. Using trans-2-nonenal (NE) as a model lipid alkenal:
* The reaction GSH + NE ⇌ GS-NE has an equilibrium constant Keq = 10.7 mM−1 (~94% product at equilibrium). (scian2023reversibilityandlow pages 9-11)
* Yet GSTA4-4 shows low “commitment to forward catalysis”: normalized kcat,ex ≈ 69 s−1 for H/D exchange at NE C2 (NMR) versus kcat,f ≈ 184 s−1 for net GS-NE formation (LC–MS), giving a forward:exchange ratio of ~2.9:1. (scian2023reversibilityandlow pages 9-11)
* Forward catalytic efficiencies were only ~16-fold (NE) and ~3-fold (GSH) greater than reverse-direction efficiency for GS-NE, consistent with substantial retro-Michael flux. (scian2023reversibilityandlow pages 11-12)
Interpretation: these kinetic properties support the view that GSTA4-4 can contribute to steady-state control of electrophilic lipid signaling molecules, not only their elimination. (scian2023reversibilityandlow pages 11-12, scian2023reversibilityandlow pages 1-3)
A rat-focused qPCR study quantified Gsta4 mRNA in Sprague–Dawley rat liver from fetal stages through aging (to 800 days). Gsta4 mRNA was low prenatally and increased after birth to adulthood; a reported high/peak level reached ~25% of β-actin (2−ΔΔCt normalization), indicating substantial hepatic transcript abundance in this dataset. (xu2018ageassociatedchangesin pages 3-4, xu2018ageassociatedchangesin pages 1-3)
Although GSTs are classically described as cytosolic, GSTA4-4 has strong evidence for mitochondrial association:
* Reviews note that treatment with 4-HNE increases mitochondrial association/translocation of GSTA4-4 in cells, consistent with stress-responsive targeting. (hayes2005glutathionetransferases. pages 9-12)
* A detailed review of mitochondrial GSTs describes GSTA4-4 detected in hepatic mitochondria (including rat liver) and also in both cytosol and mitochondria depending on experimental system. (raza2011duallocalizationof pages 2-4)
* Mechanistically, mitochondrial targeting can be activated by phosphorylation (e.g., Ser189/Thr193) and involves enhanced Hsp70 interaction, enabling import competence and increasing mitochondrial localization under oxidative/electrophilic stress (including 4-HNE exposure). (raza2011duallocalizationof pages 4-5)
Functional implication: mitochondrial GSTA4-4 is positioned to protect mitochondria from reactive aldehydes formed during oxidative stress. (raza2011duallocalizationof pages 2-4, raza2011duallocalizationof pages 4-5)
Rat liver-focused work notes that GSTA4 can be induced by Nrf2 inducers (e.g., oltipraz, ethoxyquin, butylated hydroxyanisole), consistent with ARE/Nrf2-mediated antioxidant defense programs. (xu2018ageassociatedchangesin pages 4-6)
Across mechanistic and model systems, GSTA4/GSTA4-4 sits at a central control point:
1) oxidative stress generates lipid alkenals (4-HNE/NE),
2) GSTA4-4 conjugates them with GSH (GS-HNE/GS-NE),
3) conjugation decreases electrophile burden and can also tune downstream pathways (e.g., MAPK/JNK and Nrf2/ARE). (hayes2005glutathionetransferases. pages 9-12, scian2023reversibilityandlow pages 11-12)
In obstructive nephropathy models, loss of GSTA4 accelerates injury. A Journal of Pathology study reports that GSTA4-4 has ~100-fold higher catalytic activity toward 4-HNE than other GSTs and positions 4-HNE as a key driver of tubule damage/fibrosis. In UUO, 4-HNE/adduct accumulation rises while GSTA4 expression falls; genetic deletion worsens fibrosis and autophagy, while GSTA4 overexpression prevents 4-HNE–induced autophagy and damage markers. The study also demonstrates translationally relevant in vivo gene delivery (transposon-delivered GSTA4) that suppresses UUO-induced epithelial junction loss and autophagy. (liang2012lossofglutathione pages 1-3)
In chronic ethanol exposure models, GSTA4 deletion increases reactive aldehyde damage:
* In Redox Biology (2016), ethanol-fed GSTA4-deficient mice showed 1.61-fold more carbonylated proteins in mitochondrial fractions than ethanol-fed WT; 829 carbonylated proteins were identified across fractions, linking GSTA4 to mitochondrial protection and metabolic pathway integrity. (shearn2016deletionofgsta44 pages 1-2)
* In Alcoholism: Clinical and Experimental Research (2018), a long-term ethanol feeding study (116 days; up to 28% calories as ethanol; with/without 3 g/kg binge) showed increased hepatic 4-HNE adduction and inflammation, and proteomics identified 1,022 carbonylated proteins with 189 unique to GSTA4−/− mice, supporting GSTA4 as a modifier of aldehyde-driven inflammatory remodeling. (shearn2018knockoutofthe pages 1-3)
These are widely used real-world implementations of Gsta4 biology as readouts for oxidative stress, lipid aldehyde detoxification capacity, and mitochondrial vulnerability. (shearn2016deletionofgsta44 pages 1-2, shearn2018knockoutofthe pages 1-3)
In mouse heart, Gsta4-null tissue retains only 23% of WT 4-HNE-conjugating activity yet shows strong compensatory Nrf2 activation (e.g., 2.15-fold increase in Nrf2 DNA binding; ~3-fold Sod2 mRNA; >2-fold catalase mRNA; catalase +12%, AKR +30%, ALDH +29%, total SOD +46%). In a chronic doxorubicin protocol (15 mg/kg injections; 28 days), Gsta4-null mice exhibited 87% reduction in mortality (hazard ratio 0.132, p = 0.033) relative to WT, illustrating that GSTA4 loss can provoke protective adaptation via stress-response circuitry, complicating simplistic “more GSTA4 is always better” interpretations. (benes2013protectionfromoxidative pages 6-7, benes2013protectionfromoxidative pages 1-2)
A high-citation Annual Review emphasizes that alpha-class GSTs including GSTA4-4 participate in detoxification of lipid electrophiles and can change subcellular distribution (including mitochondrial association) in response to 4-HNE, situating these enzymes at the interface of detoxification and stress signaling. (hayes2005glutathionetransferases. pages 9-12)
The 2023 Biomolecules study provides new quantitative support for a model in which GSTA4-4 helps maintain homeostatic alkenal pools by balancing forward conjugation with reverse chemistry, rather than functioning as a purely one-direction detoxification sink. This directly updates functional annotation for “primary role” from clearance-only toward clearance + signaling set-point control. (scian2023reversibilityandlow pages 11-12, scian2023reversibilityandlow pages 9-11)
A 2024 Pharmaceuticals study explicitly develops hGSTA4-4 inhibitors (translational relevance to GSTA4 biology):
* Ellagic acid: IC50 0.44 ± 0.01 µM; competitive Ki 0.39 ± 0.02 µM (vs GSH) and 0.63 ± 0.03 µM (vs CDNB). (tsouri2024amonocarbonylcurcuminoid pages 6-8, tsouri2024amonocarbonylcurcuminoid pages 8-11)
* DM151: IC50 2.4 ± 0.1 µM; competitive Ki 0.98 ± 0.11 µM (vs GSH); mixed inhibition vs CDNB (Ki 4.1 ± 0.5 µM, Ki′ 0.53 ± 0.03 µM). (tsouri2024amonocarbonylcurcuminoid pages 8-11)
* Docking affinities (arbitrary units): ellagic acid −45.18, DM151 −44.59, DM101 −36.37, DM100 −33.37, with key interactions involving Arg15/Tyr9/Phe111/Phe220. (tsouri2024amonocarbonylcurcuminoid pages 8-11, tsouri2024amonocarbonylcurcuminoid pages 11-12)
* Cell implementation: after 48 h, DM151 showed glioblastoma IC50 values 25.57 ± 4.83 µM (U251-MG) and 18.95 ± 5.81 µM (U87-MG), whereas weak inhibitor DM148 had ~89–91 µM IC50; the paper cites temozolomide median IC50 223.1 µM in U-87 MG as contextual comparator. (tsouri2024amonocarbonylcurcuminoid pages 11-12)
While this is human enzyme work, it is a concrete 2024 example of real-world implementation (drug discovery/chemosensitization) built on the same conserved GSTA4-4 biochemical function. (tsouri2024amonocarbonylcurcuminoid pages 8-11, tsouri2024amonocarbonylcurcuminoid pages 11-12)
The table below compiles enzyme function, substrates, localization, regulation, pathway roles, and 2023–2024 quantitative advances.
| Annotation aspect | Key points | Best supporting citations |
|---|---|---|
| Enzyme class / target identity | Rat Gsta4 in the UniProt P14942 context corresponds to glutathione S-transferase alpha-4 (GSTA4-4), an alpha-class cytosolic GST within the GST superfamily. Literature consistently discusses GSTA4-4 as the alpha-class GST specialized for detoxifying lipid peroxidation-derived alkenals, though the accession-level mapping to P14942 was not explicit in the retrieved full text and remains primarily a UniProt/database verification point. | (hayes2005glutathionetransferases. pages 9-12, hayes2005glutathionetransferases. pages 19-21, lv2023overexpressionofglutathione pages 1-2) |
| Catalyzed reaction | The core reaction is glutathione conjugation of electrophilic lipid alkenals by Michael addition: GSH + alkenal ⇌ GS-alkenal. For 4-HNE and related substrates, GSTA4-4 forms glutathionylated adducts such as GS-HNE/GS-NE, supporting phase II detoxification and control of reactive aldehyde signaling. | (scian2023reversibilityandlow pages 11-12, scian2023reversibilityandlow pages 1-3, lv2023overexpressionofglutathione pages 2-4) |
| Key substrates / specificity | GSTA4-4 shows marked preference for 4-hydroxynonenal (4-HNE) and related lipid-derived α,β-unsaturated aldehydes such as 4-hydroxydecenal and trans-2-nonenal. Compared with the more promiscuous GSTA1-1, GSTA4-4 is described as highly chemoselective for these toxic lipid peroxidation products, with ~50-fold lower kcat/Km for HNE in GSTA1-1 than in GSTA4-4. | (balogh2010substratespecificitycombined pages 1-2, hayes2005glutathionetransferases. pages 9-12) |
| Stereochemistry / product formation | GSTA4-4 accepts both 4R- and 4S-HNE with little substrate stereoselectivity but still enforces stereoselective product formation, generating 3S-glutathionyl-4-hydroxynonanal adducts. This combination of substrate stereopromiscuity and product stereoselectivity appears to arise from a pre-organized active site rather than induced fit. | (balogh2010substratespecificitycombined pages 1-2) |
| Mechanism / structure notes | Cytosolic GSTs have the canonical GST architecture with an N-terminal G-site for GSH and a C-terminal H-site for hydrophobic electrophiles. For GSTA4-4 specifically, mechanistic studies highlight an unusually acidic/unprotonated Tyr9, limited ligand-induced conformational change, and a rigid C-terminal region that help explain high alkenal specificity and catalytic behavior. | (scian2023reversibilityandlow pages 1-3, scian2023reversibilityandlow pages 3-4, lv2023overexpressionofglutathione pages 2-4) |
| Reversibility / homeostatic role | Recent work shows GSTA4-4 is not simply a one-way detoxification enzyme: it also catalyzes the retro-Michael reaction, regenerating alkenal and GSH from GS-alkenal. For NE, the equilibrium constant was reported as Keq = 10.7 mM−1 (~94% product at equilibrium), but kinetic partitioning still showed substantial reversibility, supporting a possible homeostatic/regulatory role in maintaining signaling alkenal pools. | (scian2023reversibilityandlow pages 11-12, scian2023reversibilityandlow pages 9-11, scian2023reversibilityandlow pages 12-14) |
| Quantitative catalytic data | In 2023 mechanistic work, normalized kcat,ex for GSTA4-4-mediated NE deuteration was 69 s−1, while forward kcat,f for GS-NE formation was ~184 s−1, yielding a forward:exchange ratio of about 2.9:1. The forward kcat/KM values for NE and GSH were only ~16-fold and ~3-fold larger than the reverse-direction kcat,r/KM for GS-NE, indicating low commitment to forward catalysis. | (scian2023reversibilityandlow pages 11-12, scian2023reversibilityandlow pages 9-11) |
| Subcellular localization | Functionally, GSTA4-4 is best known as a cytosolic GST, but multiple studies also support mitochondrial localization. In liver and brain systems, GSTA4-4 has been detected in both cytosol and mitochondria, and oxidative/electrophilic stress can increase its mitochondrial association, consistent with a role in protecting mitochondria from lipid aldehydes. | (hayes2005glutathionetransferases. pages 9-12, raza2011duallocalizationof pages 2-4, raza2011duallocalizationof pages 4-5) |
| Mitochondrial targeting mechanism | Mitochondrial import of GSTA4-4 appears to involve a cryptic C-terminal targeting signal and stress-responsive phosphorylation. Ser189 and Thr193 were identified as phosphorylation sites required to activate the import signal, and hyperphosphorylation promotes Hsp70 interaction and mitochondrial targeting. | (raza2011duallocalizationof pages 4-5) |
| Regulation by oxidative stress pathways | GSTA4 is inducible by oxidative-stress pathways, especially Nrf2/ARE. In rat liver-focused work, Gsta4 expression increased with age to adulthood and was reported inducible by Nrf2 activators such as oltipraz, ethoxyquin, and butylated hydroxyanisole; related studies also implicate CAR/PXR and, in mouse hepatocytes, JNK signaling during oxidative-stress induction. | (xu2018ageassociatedchangesin pages 4-6, xu2018ageassociatedchangesin pages 7-7, xu2018ageassociatedchangesin pages 1-3) |
| Rat liver developmental / age expression | In rat liver, Gsta4 mRNA was measured across fetal to aged stages and showed a pattern of gradual increase after birth to adulthood, with slight decline only at the oldest time points in one summary and high levels still evident in another quantitative description. A reported peak/high value reached about 25.0% of β-actin by qPCR normalization, making Gsta4 one of the more abundant GST-family transcripts in this dataset. | (xu2018ageassociatedchangesin pages 3-4, xu2018ageassociatedchangesin pages 1-3) |
| Physiological role | The best-supported biological role is detoxification of reactive lipid aldehydes, especially 4-HNE, thereby limiting protein carbonylation, oxidative damage, and downstream stress signaling. This places GSTA4 in pathways of lipid peroxidation defense, redox homeostasis, and protection of vulnerable compartments such as mitochondria. | (hayes2005glutathionetransferases. pages 9-12, shearn2016deletionofgsta44 pages 1-2) |
| Phenotypic evidence from loss-of-function models | Genetic loss of Gsta4 in mouse models generally increases susceptibility to aldehyde adduction and tissue injury. Examples include accelerated renal fibrosis, increased hepatic protein carbonylation, broader mitochondrial aldehyde-mediated protein modification after ethanol exposure, and reduced 4-HNE-conjugating capacity in heart tissue. | (shearn2016deletionofgsta44 pages 1-2, benes2013protectionfromoxidative pages 6-7) |
| Compensatory stress responses | In Gsta4-null mouse heart, loss of GSTA4 triggered compensatory antioxidant activation rather than simple collapse of defense systems. Reported changes included 2.15-fold higher Nrf2 DNA binding (p = 0.0002), ~3-fold higher Sod2 mRNA, >2-fold higher catalase mRNA, and higher catalase (+12%), AKR (+30%), ALDH (+29%), and total SOD (+46%) activities. | (benes2013protectionfromoxidative pages 6-7) |
| Disease and signaling relevance | Because 4-HNE is both toxic and signaling-active, GSTA4-4 affects not only detoxification but also stress signaling outputs such as JNK, apoptosis, and Nrf2-dependent responses. Reviews and mechanistic studies therefore frame GSTA4 as an enzyme at the interface of damage control and redox signaling calibration. | (scian2023reversibilityandlow pages 11-12, mazari2023themultifacetedrole pages 4-6) |
| 2023-2024 development: revised conceptual model | A notable 2023 development is the proposal that GSTA4-4 helps set steady-state alkenal concentrations rather than merely destroying them. The low commitment to forward catalysis and enzyme-catalyzed reverse chemistry support a revised view of GSTA4-4 as a regulatory/homeostatic node in lipid aldehyde metabolism. | (scian2023reversibilityandlow pages 11-12, scian2023reversibilityandlow pages 1-3) |
| 2024 therapeutic targeting / inhibition | A 2024 study directly targeted hGSTA4-4 with small molecules, supporting translational interest in this enzyme. Ellagic acid inhibited hGSTA4-4 with IC50 = 0.44 ± 0.01 µM and competitive Ki = 0.39 ± 0.02 µM vs GSH and 0.63 ± 0.03 µM vs CDNB; DM151 had IC50 = 2.4 ± 0.1 µM, competitive Ki = 0.98 ± 0.11 µM vs GSH, and mixed inhibition vs CDNB with Ki = 4.1 ± 0.5 µM and Ki′ = 0.53 ± 0.03 µM. | (tsouri2024amonocarbonylcurcuminoid pages 6-8, tsouri2024amonocarbonylcurcuminoid pages 8-11) |
| 2024 docking / binding data | Docking in the same 2024 study ranked inhibitors by affinity for hGSTA4-4: ellagic acid −45.18, DM151 −44.59, DM101 −36.37, DM100 −33.37 (arbitrary units). These results aligned with biochemical inhibition data and indicated that potent inhibitors occupy the G-site/N-terminal region, with key contacts involving Arg15, Tyr9, Phe111, and Phe220. | (tsouri2024amonocarbonylcurcuminoid pages 8-11, tsouri2024amonocarbonylcurcuminoid pages 11-12) |
| 2024 cell-based implementation | In glioblastoma cell models overexpressing hGSTA4-4, DM151 was markedly more cytotoxic than weak inhibitor DM148 after 48 h: U251-MG IC50 25.57 ± 4.83 µM vs 89.21 ± 3.41 µM and U87-MG IC50 18.95 ± 5.81 µM vs 91.09 ± 5.64 µM. The study also argues these values compare favorably with reported temozolomide median IC50 = 223.1 µM in U-87 MG cells, supporting GSTA4 inhibition as a chemosensitization strategy. | (tsouri2024amonocarbonylcurcuminoid pages 11-12) |
Table: This table summarizes the strongest evidence gathered for rat Gsta4/GST alpha-4 in the UniProt P14942 context, emphasizing enzymatic function, substrates, localization, regulation, and recent 2023-2024 developments. It is designed as a compact annotation aid with quantitative values and direct context-ID citations for traceability.
Molecular function: cytosolic/mitochondria-associated glutathione transferase catalyzing GSH conjugation of lipid peroxidation-derived α,β-unsaturated aldehydes (especially 4-HNE) by Michael addition; capable of catalyzing reverse (retro-Michael) reactions with some GS-alkenal adducts, supporting a potential homeostatic signaling role. (scian2023reversibilityandlow pages 11-12, balogh2010substratespecificitycombined pages 1-2, hayes2005glutathionetransferases. pages 9-12)
Biological process: detoxification of reactive lipid aldehydes; limitation of protein carbonylation and oxidative stress damage; modulation of stress-response pathways including MAPKs/JNK and Nrf2-linked adaptive programs. (liang2012lossofglutathione pages 1-3, scian2023reversibilityandlow pages 11-12, mcelhanon2013gsta4nullmouse pages 6-7)
Cellular component: primarily cytosolic enzyme with stress-inducible mitochondrial targeting/association; mitochondrial import can be phosphorylation/Hsp70-dependent. (raza2011duallocalizationof pages 2-4, raza2011duallocalizationof pages 4-5)
Because the retrieved full texts did not explicitly mention UniProt P14942 nor all UniProt-listed synonyms (GST 8-8, GST K, GST Yk) in the same context, accession-level confirmation and alias mapping should be completed using UniProt/InterPro records (outside the retrieved corpus). The functional and mechanistic conclusions above are nonetheless tightly anchored to the GSTA4-4 alpha-class GST entity defined by its highly characteristic substrate preference for 4-HNE and related lipid alkenals. (balogh2010substratespecificitycombined pages 1-2, hayes2005glutathionetransferases. pages 9-12)
References
(hayes2005glutathionetransferases. pages 9-12): John D. Hayes, Jack U. Flanagan, and Ian R. Jowsey. Glutathione transferases. Annual review of pharmacology and toxicology, 45:51-88, Sep 2005. URL: https://doi.org/10.1146/annurev.pharmtox.45.120403.095857, doi:10.1146/annurev.pharmtox.45.120403.095857. This article has 5223 citations and is from a highest quality peer-reviewed journal.
(hayes2005glutathionetransferases. pages 19-21): John D. Hayes, Jack U. Flanagan, and Ian R. Jowsey. Glutathione transferases. Annual review of pharmacology and toxicology, 45:51-88, Sep 2005. URL: https://doi.org/10.1146/annurev.pharmtox.45.120403.095857, doi:10.1146/annurev.pharmtox.45.120403.095857. This article has 5223 citations and is from a highest quality peer-reviewed journal.
(lv2023overexpressionofglutathione pages 2-4): Ning Lv, Chunyan Huang, Haoyan Huang, Zhiqiang Dong, Xijing Chen, Chengcan Lu, and Yongjie Zhang. Overexpression of glutathione s-transferases in human diseases: drug targets and therapeutic implications. Antioxidants, 12:1970, Nov 2023. URL: https://doi.org/10.3390/antiox12111970, doi:10.3390/antiox12111970. This article has 53 citations.
(balogh2010substratespecificitycombined pages 1-2): Larissa M. Balogh, Isolde Le Trong, Kimberly A. Kripps, Laura M. Shireman, Ronald E. Stenkamp, Wei Zhang, Bengt Mannervik, and William M. Atkins. Substrate specificity combined with stereopromiscuity in glutathione transferase a4-4-dependent metabolism of 4-hydroxynonenal. Biochemistry, 49 7:1541-8, Feb 2010. URL: https://doi.org/10.1021/bi902038u, doi:10.1021/bi902038u. This article has 53 citations and is from a peer-reviewed journal.
(scian2023reversibilityandlow pages 9-11): Michele Scian, Lorela Paço, Taylor A. Murphree, Laura M. Shireman, and William M. Atkins. Reversibility and low commitment to forward catalysis in the conjugation of lipid alkenals by glutathione transferase a4-4. Biomolecules, 13:329, Feb 2023. URL: https://doi.org/10.3390/biom13020329, doi:10.3390/biom13020329. This article has 6 citations.
(scian2023reversibilityandlow pages 11-12): Michele Scian, Lorela Paço, Taylor A. Murphree, Laura M. Shireman, and William M. Atkins. Reversibility and low commitment to forward catalysis in the conjugation of lipid alkenals by glutathione transferase a4-4. Biomolecules, 13:329, Feb 2023. URL: https://doi.org/10.3390/biom13020329, doi:10.3390/biom13020329. This article has 6 citations.
(scian2023reversibilityandlow pages 1-3): Michele Scian, Lorela Paço, Taylor A. Murphree, Laura M. Shireman, and William M. Atkins. Reversibility and low commitment to forward catalysis in the conjugation of lipid alkenals by glutathione transferase a4-4. Biomolecules, 13:329, Feb 2023. URL: https://doi.org/10.3390/biom13020329, doi:10.3390/biom13020329. This article has 6 citations.
(xu2018ageassociatedchangesin pages 3-4): Shangfu Xu, Dong-Shun Hou, Jie Liu, and Lili Ji. Age-associated changes in gsh s-transferase gene/proteins in livers of rats. Redox Report : Communications in Free Radical Research, 23:213-218, Jan 2018. URL: https://doi.org/10.1080/13510002.2018.1546985, doi:10.1080/13510002.2018.1546985. This article has 30 citations.
(xu2018ageassociatedchangesin pages 1-3): Shangfu Xu, Dong-Shun Hou, Jie Liu, and Lili Ji. Age-associated changes in gsh s-transferase gene/proteins in livers of rats. Redox Report : Communications in Free Radical Research, 23:213-218, Jan 2018. URL: https://doi.org/10.1080/13510002.2018.1546985, doi:10.1080/13510002.2018.1546985. This article has 30 citations.
(raza2011duallocalizationof pages 2-4): Haider Raza. Dual localization of glutathione s‐transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. The FEBS Journal, 278:4243-4251, Nov 2011. URL: https://doi.org/10.1111/j.1742-4658.2011.08358.x, doi:10.1111/j.1742-4658.2011.08358.x. This article has 326 citations.
(raza2011duallocalizationof pages 4-5): Haider Raza. Dual localization of glutathione s‐transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. The FEBS Journal, 278:4243-4251, Nov 2011. URL: https://doi.org/10.1111/j.1742-4658.2011.08358.x, doi:10.1111/j.1742-4658.2011.08358.x. This article has 326 citations.
(xu2018ageassociatedchangesin pages 4-6): Shangfu Xu, Dong-Shun Hou, Jie Liu, and Lili Ji. Age-associated changes in gsh s-transferase gene/proteins in livers of rats. Redox Report : Communications in Free Radical Research, 23:213-218, Jan 2018. URL: https://doi.org/10.1080/13510002.2018.1546985, doi:10.1080/13510002.2018.1546985. This article has 30 citations.
(liang2012lossofglutathione pages 1-3): Anlin Liang, Yun Wang, Lauren E Woodard, Matthew H Wilson, Rajendra Sharma, Yogesh C Awasthi, Jie Du, William E Mitch, and Jizhong Cheng. Loss of glutathione s‐transferase a4 accelerates obstruction‐induced tubule damage and renal fibrosis. The Journal of Pathology, 228:448-458, Dec 2012. URL: https://doi.org/10.1002/path.4067, doi:10.1002/path.4067. This article has 41 citations.
(shearn2016deletionofgsta44 pages 1-2): Colin T. Shearn, Kristofer S. Fritz, Alisabeth H. Shearn, Laura M. Saba, Kelly E. Mercer, Bridgette Engi, James J. Galligan, Piotr Zimniak, David J. Orlicky, Martin J. Ronis, and Dennis R. Petersen. Deletion of gsta4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice. Redox Biology, 7:68-77, Apr 2016. URL: https://doi.org/10.1016/j.redox.2015.11.013, doi:10.1016/j.redox.2015.11.013. This article has 51 citations and is from a domain leading peer-reviewed journal.
(shearn2018knockoutofthe pages 1-3): Colin T. Shearn, Casey F. Pulliam, Kim Pedersen, Kyle Meredith, Kelly E. Mercer, Laura M. Saba, David J. Orlicky, Martin J. Ronis, and Dennis R. Petersen. Knockout of the gsta4 gene in male mice leads to an altered pattern of hepatic protein carbonylation and enhanced inflammation following chronic consumption of an ethanol diet. Alcoholism: Clinical and Experimental Research, 42:1192–1205, May 2018. URL: https://doi.org/10.1111/acer.13766, doi:10.1111/acer.13766. This article has 19 citations.
(benes2013protectionfromoxidative pages 6-7): Helen Beneš, Mai K. Vuong, Marjan Boerma, Kevin E. McElhanon, Eric R. Siegel, and Sharda P. Singh. Protection from oxidative and electrophilic stress in the gsta4-null mouse heart. Cardiovascular Toxicology, 13:347-356, May 2013. URL: https://doi.org/10.1007/s12012-013-9215-1, doi:10.1007/s12012-013-9215-1. This article has 21 citations and is from a peer-reviewed journal.
(benes2013protectionfromoxidative pages 1-2): Helen Beneš, Mai K. Vuong, Marjan Boerma, Kevin E. McElhanon, Eric R. Siegel, and Sharda P. Singh. Protection from oxidative and electrophilic stress in the gsta4-null mouse heart. Cardiovascular Toxicology, 13:347-356, May 2013. URL: https://doi.org/10.1007/s12012-013-9215-1, doi:10.1007/s12012-013-9215-1. This article has 21 citations and is from a peer-reviewed journal.
(tsouri2024amonocarbonylcurcuminoid pages 6-8): Steliana Tsouri, Evanthia Tselo, Georgios E. Premetis, Veronika Furlan, Panagiota D. Pantiora, Barbara Mavroidi, Dimitris Matiadis, Maria Pelecanou, Anastassios C. Papageorgiou, Urban Bren, Marina Sagnou, and Nikolaos E. Labrou. A monocarbonyl curcuminoid derivative inhibits the activity of human glutathione transferase a4-4 and chemosensitizes glioblastoma cells to temozolomide. Pharmaceuticals, 17:365, Mar 2024. URL: https://doi.org/10.3390/ph17030365, doi:10.3390/ph17030365. This article has 5 citations.
(tsouri2024amonocarbonylcurcuminoid pages 8-11): Steliana Tsouri, Evanthia Tselo, Georgios E. Premetis, Veronika Furlan, Panagiota D. Pantiora, Barbara Mavroidi, Dimitris Matiadis, Maria Pelecanou, Anastassios C. Papageorgiou, Urban Bren, Marina Sagnou, and Nikolaos E. Labrou. A monocarbonyl curcuminoid derivative inhibits the activity of human glutathione transferase a4-4 and chemosensitizes glioblastoma cells to temozolomide. Pharmaceuticals, 17:365, Mar 2024. URL: https://doi.org/10.3390/ph17030365, doi:10.3390/ph17030365. This article has 5 citations.
(tsouri2024amonocarbonylcurcuminoid pages 11-12): Steliana Tsouri, Evanthia Tselo, Georgios E. Premetis, Veronika Furlan, Panagiota D. Pantiora, Barbara Mavroidi, Dimitris Matiadis, Maria Pelecanou, Anastassios C. Papageorgiou, Urban Bren, Marina Sagnou, and Nikolaos E. Labrou. A monocarbonyl curcuminoid derivative inhibits the activity of human glutathione transferase a4-4 and chemosensitizes glioblastoma cells to temozolomide. Pharmaceuticals, 17:365, Mar 2024. URL: https://doi.org/10.3390/ph17030365, doi:10.3390/ph17030365. This article has 5 citations.
(lv2023overexpressionofglutathione pages 1-2): Ning Lv, Chunyan Huang, Haoyan Huang, Zhiqiang Dong, Xijing Chen, Chengcan Lu, and Yongjie Zhang. Overexpression of glutathione s-transferases in human diseases: drug targets and therapeutic implications. Antioxidants, 12:1970, Nov 2023. URL: https://doi.org/10.3390/antiox12111970, doi:10.3390/antiox12111970. This article has 53 citations.
(scian2023reversibilityandlow pages 3-4): Michele Scian, Lorela Paço, Taylor A. Murphree, Laura M. Shireman, and William M. Atkins. Reversibility and low commitment to forward catalysis in the conjugation of lipid alkenals by glutathione transferase a4-4. Biomolecules, 13:329, Feb 2023. URL: https://doi.org/10.3390/biom13020329, doi:10.3390/biom13020329. This article has 6 citations.
(scian2023reversibilityandlow pages 12-14): Michele Scian, Lorela Paço, Taylor A. Murphree, Laura M. Shireman, and William M. Atkins. Reversibility and low commitment to forward catalysis in the conjugation of lipid alkenals by glutathione transferase a4-4. Biomolecules, 13:329, Feb 2023. URL: https://doi.org/10.3390/biom13020329, doi:10.3390/biom13020329. This article has 6 citations.
(xu2018ageassociatedchangesin pages 7-7): Shangfu Xu, Dong-Shun Hou, Jie Liu, and Lili Ji. Age-associated changes in gsh s-transferase gene/proteins in livers of rats. Redox Report : Communications in Free Radical Research, 23:213-218, Jan 2018. URL: https://doi.org/10.1080/13510002.2018.1546985, doi:10.1080/13510002.2018.1546985. This article has 30 citations.
(mazari2023themultifacetedrole pages 4-6): Aslam M. A. Mazari, Leilei Zhang, Zhi-Wei Ye, Jie Zhang, Kenneth D. Tew, and Danyelle M. Townsend. The multifaceted role of glutathione s-transferases in health and disease. Biomolecules, 13:688, Apr 2023. URL: https://doi.org/10.3390/biom13040688, doi:10.3390/biom13040688. This article has 238 citations.
(mcelhanon2013gsta4nullmouse pages 6-7): Kevin E. McElhanon, Chhanda Bose, Rajendra Sharma, Liping Wu, Yogesh C. Awasthi, and Sharda P. Singh. Gsta4 null mouse embryonic fibroblasts exhibit enhanced sensitivity to oxidants: role of 4-hydroxynonenal in oxidant toxicity. Open journal of apoptosis, 2 1:1-11, Jan 2013. URL: https://doi.org/10.4236/ojapo.2013.21001, doi:10.4236/ojapo.2013.21001. This article has 46 citations.