Ask about this productRelated genes to: GSTA1 protein
- Gene:
- GSTA1 NIH gene
- Name:
- glutathione S-transferase alpha 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 6p12.2
- Locus Type:
- gene with protein product
- Date approved:
- 1991-12-06
- Date modifiied:
- 2015-09-10
Related products to: GSTA1 protein
Related articles to: GSTA1 protein
- Bacterial infections contribute to many human diseases and cancer development, and their increasing incidence, together with rising antimicrobial resistance, underscores the urgent need for new potent biologically active compounds. Quantitative structure-activity relationship (QSAR) modeling was conducted to evaluate a series of oxazole derivatives as antibacterials. Eighteen new 5-amino-4-cyano-1,3-oxazoles with promising predictive properties were synthesized and reliably characterized. Fourteen compounds were found to inhibit bacterial growth (MICs varied from 8 to 512 µg/mL). Eight derivatives exhibited the highest activity against colistin-resistant Escherichia coli and Staphylococcus aureus isolates with MICs of 8-64 µg/mL. Moreover, six compounds exhibited activities greater or similar to that of reference oxacillin and cefepime against clinical isolates. Analysis of the studied 5-amino-4-cyano-1,3-oxazoles as target-directed glutathione S-transferase (GST) inhibitors showed that derivatives 7, 11, and 12 inhibited GSTA1-1 with an IC range of 3.2-7.5 µM. Molecular docking results indicate that these compounds can occupy the enzyme's active site. The cytotoxicity results in L20B and RD cell lines showed that compounds 11 and 12 demonstrated significant cytostatic effects, with CD values ranging from 0.02 to 2 µg/mL. Additionally, these two compounds showed moderate acute toxicity toward D. magna, with LC values of 7.27 ± 1.22 and 5.10 ± 1.07 mg/L (D.R. Passino classification). - Source: PubMed
Hodyna DianaKachaeva MarynaShulha YuriiTrokhimenko OlenaKovalishyn VasylBrovarets VolodymyrMetelytsia Larysa - Chlorfenapyr (CFP) is a halogenated pyrrole insecticide that requires metabolic activation to exert toxicity and has been associated with severe poisoning in humans. However, the metabolic pathways underlying CFP bioactivation and detoxification in humans remain poorly defined. In this study, we systematically investigated the metabolic fate of CFP and its toxic metabolite tralopyril (TLP) using in vitro human drug-metabolizing enzyme systems. Screening of ten human cytochrome P450 (CYP) isoforms at 5 and 50 µM CFP indicated that CYP2B6 is the major contributor to CFP bioactivation, which was further supported by selective inhibition and correlation analyses. CFP metabolism by CYP2B6 followed Michaelis-Menten kinetics, with showing a K of 1.80 ± 0.57 μM, a V of 0.24 ± 0.02 pmol/min/pmol P450, and an CL of 139.78 ± 33.70 nL/min/pmol P450. In addition, incubations using 50 or 100 µM TLP and varying concentrations of glutathione (0.1 to 1 mM GSH) showed the formation of a novel GSH conjugate of TLP (TLP-GSH), of which level was markedly enhanced by human glutathione S-transferases (GSTs). Among six recombinant human GST isoforms tested, GSTA1, GSTA2, GSTM1, and GSTP1 showed significant catalytic activity in TLP-GSH formation compared with non-enzymatic reactions. Moreover, extracellular flux analysis revealed that TLP dose-dependently inhibited basal and maximal oxygen consumption rates, an effect exacerbated by GST inhibition, indicating a protective role of GSTs in TLP-induced mitochondrial toxicity. Together, these findings delineated metabolic enzymes-mediated bioactivation and detoxification pathways governing CFP toxicity in humans and provided a new perspective on clinical management strategies for CFP poisoning. - Source: PubMed
Publication date: 2026/04/15
Deng LiYan HanwenQian ZhipengZhong JiaqiXie WenpeiWang JianfengXu JunGao HongZong LiangChen XijingHuang HaoyanZhang Yongjie - : Piperine, an alkaloid from , modulates oxidative stress, proliferation, and survival pathways in several cancer models; however, its mechanistic effects in colorectal epithelial Caco-2 cells remain insufficiently defined. : This study aimed to investigate the cytotoxic, antiproliferative, oxidative, autophagic, and anti-migratory effects of piperine in Caco-2 cells. : Caco-2 cells were treated with piperine (0.001-0.1 mg/mL) for up to 72 h. Cell viability, proliferation, and migration were assessed using SRB and scratch assays. Oxidative stress, apoptosis, autophagy, and tight junction integrity were evaluated through ROS quantification, Western blotting, gene expression analysis, confocal microscopy, and transmission electron microscopy (TEM). NACET was used to determine the contribution of oxidative stress to piperine-induced cytotoxicity and autophagy. : Piperine induced a time- and dose-dependent reduction in viability, with viability decreasing to 53.0 ± 2.88% at 0.1 mg/mL after 72 h. Proliferation decreased to 51% of control levels ( < 0.001), accompanied by p21 upregulation ( < 0.05), indicating G2/M cell cycle arrest. Piperine markedly increased intracellular ROS ( < 0.001), downregulated NRF2 ( < 0.05), and suppressed expression ( < 0.001), while NACET co-treatment restored viability ( < 0.001). No activation of caspase-dependent apoptosis was observed. Piperine significantly enhanced autophagic flux, as shown by the increased LC3B-II/LC3B-I ratio ( < 0.01), elevated LC3B-II/LAMP-1 co-localization ( < 0.01), and chloroquine-induced accumulation of LC3B-II and p62 ( < 0.01), with preserved lysosomal function. TEM analysis confirmed a marked increase in double-membrane autophagosomes in piperine-treated cells compared with controls. NACET reduced LC3B-II/LC3B-I levels, increased p21 expression, and significantly improved cell viability, indicating that piperine-induced autophagy is cytotoxic and driven by oxidative stress. Additionally, piperine upregulated occludin ( < 0.01) and reduced cell migration independently of proliferation ( < 0.01). : Piperine exerts antiproliferative effects in Caco-2 cells through ROS-mediated stress, p21-dependent G2/M arrest, and activation of cytotoxic autophagy. Its ability to impair migration and enhance tight junction integrity further supports its potential as a complementary therapeutic agent in colon cancer. - Source: PubMed
Publication date: 2026/03/27
Sudan HlaPassaponti SofiaCasini IleniaRomagnoli RobertaCresti LauraGentile MariangelaFrosini MariaAloisi Anna Maria - The incorporation of water disinfectants into the main water supply has significantly decreased the incidence of waterborne diseases. However, the interaction between disinfectants and organic material generates water disinfection byproducts (DBPs) such as iodoacetic acid (IAA). IAA is an ovarian toxicant, but little is known about its mechanisms of toxicity. Thus, we tested the hypothesis that IAA exposure causes ovarian toxicity through oxidative stress pathways. Adult CD-1 mice were dosed with vehicle control (reverse osmosis water) or IAA (2.7- 2,695.7 μM) for 35 days. Then, whole ovaries or isolated antral follicles were collected for measurement of expression of several enzymes that regulate oxidative stress (Gpx1, Gpx2, Gsr, Gss, Gsta1, Gstm1, Gsto1, Gstp1 Gstt1, Sod1, Sod2, and Cat). In other experiments, antral follicles were cultured with vehicle control ± the antioxidant Trolox or IAA (2-15 μM) ± the antioxidant Trolox for 96 hours and follicle growth was measured every 24 hours. Media were collected for estradiol measurements. IAA decreased Cat, Sod1, Gss, Gsta1, Gstp1, and Gstt1 and increased Gstm1 expression in whole ovaries compared to control in vivo. IAA decreased Sod2 and Gpx2 and increased Gstp1 expression in antral follicles compared to control in vivo. IAA increased Gpx1 and Gsto1 expression in antral follicles compared to control in vitro. IAA inhibited follicle growth and reduced estradiol levels, whereas Trolox rescued follicles from IAA-induced inhibition of follicle growth and estrogen levels in vitro. Collectively, these data indicate that IAA exposure causes ovarian toxicity by altering oxidative stress pathways in the mouse ovary. - Source: PubMed
Publication date: 2026/04/08
Fields Audrey LGonsioroski Andressa VarellaMárquez Ramsés SantacruzLaws Mary JFlaws Jodi A - This study aimed to investigate the effects and potential mechanisms of dietary glycerol monodecanoate (GMD) supplementation on gastrointestinal inflammation and oxidative stress in Yanbian cattle fed a high-concentrate diet. - Source: PubMed
Publication date: 2026/04/02
Xin FengLiu XinyuFang ShibinLiu YutongYang XiaoxueLin LingzhuDai YunDong TianyuDu XinLuan JiamingGeng Chunyin