Disease relevance of Glrx1

• We compared the specific activity of thioltransferase, protein disulfide isomerase, and other GSH-related enzymes in Adriamycin-resistant human breast tumor cells, MCF-7 ADRR, and Adriamycin-sensitive, MCF-7 WT, tumor cells [1].
• We have designed a new assay method to quantify the rate of reduction of GSSG and other disulfides by reduced lipoamide and have tested a set of eight recombinant Grx from human, rat, yeast, and E. coli [2].
• Localization of glutaredoxin (thioltransferase) in the rat brain and possible functional implications during focal ischemia [3].

High impact information on Glrx1

• Redox control of exocytosis: regulatory role of NADPH, thioredoxin, and glutaredoxin [4].
• We propose that the NADPH/GRX/TRX redox regulation mediates a novel signaling pathway of nutrient-induced insulin secretion [4].
• Overexpression of catalase, a dominant-negative p47(phox), or glutaredoxin-1 decreased GSS-Ras, Ras activation, p38, and Akt phosphorylation and the induction of protein synthesis by AII [5].
• Furthermore an in vitro assay revealed that GRX reduced oxidized Akt in concert with glutathione, NADPH, and glutathione-disulfide reductase [6].
• GRX functions via a disulfide exchange reaction by utilizing the active site Cys-Pro-Tyr-Cys [6].

Biological context of Glrx1

• Here we demonstrated that overexpression of GRX protected cells from hydrogen peroxide (H2O2)-induced apoptosis by regulating the redox state of Akt [6].
• Overexpression of GRX protected Akt from H2O2-induced oxidation and suppressed recruitment of protein phosphatase 2A to Akt, resulting in a sustained phosphorylation of Akt and inhibition of apoptosis [6].
• Grx immunostaining in the CL was strong in infiltrating macrophages and in a population of steroidogenic cells that survived the apoptotic burst in regressing CL and in CL remnants, but was faint or absent in young CL of the current cycle and in CL during pseudopregnancy [7].
• Thioltransferase in human red blood cells: kinetics and equilibrium [8].
• Glutaredoxin is an important enzyme in thiol homeostasis [9].

Anatomical context of Glrx1

• Grx was absent from the oocytes in the first days of postnatal life when marked oocyte degeneration takes place, but its presence was very conspicuous in the cytoplasm of oocytes in healthy and attretic follicles in rats from 10 days of age onward, independently of the day of oestrous cycle [7].
• We have found a prominent presence of Grx in the oocytes and in corpora lutea (CL) during developmental and oestrous cycle changes [7].
• These results support a role of Grx in the maintenance of functional oocytes and in luteal cells surviving the regression process, probably as a consequence of the demonstrated deglutathionylating function of this protein in an antioxidant and antiapoptotic context [7].
• Grx has been identified in brain cytosol, but the presence of activity in subcellular organelles has not been reported [10].
• The data presented demonstrate that mitochondria contain functional Grx-like activity [10].

Associations of Glrx1 with chemical compounds

• This effect was reversed by cadmium, an inhibitor of GRX [6].
• Glutaredoxin (GRX) is a small dithiol protein involved in various cellular functions, including the redox regulation of certain enzyme activities [6].
• Glutaredoxin (Grx) is a specific and efficient catalyst of glutathione-dependent deglutathionylation of protein-SS-glutathione mixed disulfides [10].
• Grx-like activity in the P1 supernatant from rat brain and liver was doubled in the presence of Triton-X 100 suggesting a releasable pool of Grx [10].
• The cholesterol 7 alpha-hydroxylase stimulatory protein could not be replaced by the thioltransferase-dependent disulfide-reducing system nor by glutathione S-transferase A, B, or C [11].

Other interactions of Glrx1

• Enzymatic catalysis by two different enzymes (glutaredoxin and thioredoxin-like) greatly enhanced the dethiolation rate [12].
• Thioltransferase, protein disulfide isomerase and thioredoxin reductase activities in livers of male and female rats were unchanged with aging, while glutathione disulfide (GSSG) reductase activity remained the same (in male livers) or increased (in female livers) as a consequence of aging [13].

Analytical, diagnostic and therapeutic context of Glrx1

• We have also performed a quantitative analysis of Grx by ELISA and Western blotting in homogenates of whole ovaries of cycling and pseudopregnant rats [7].
• A protein, previously designated thioltransferase (Askelof, P., Axelsson, K., Eriksson, S., and Mannervik, B. (1974) FEBS Lett. 38, 263-267) was purified to homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and flatbed gel isoelectric focusing [14].
• After gel filtration of cytosol on Sephadex G-100 SF, dehydroascorbate reductase activity was recovered in two distinct peaks, one corresponding to glutaredoxin (an enzyme already known for its dehydroascorbate reductase activity) and another, much larger one, corresponding to a novel enzyme different from glutaredoxin [15].
• We investigated the distribution of glutaredoxin (GRX, thioltransferase) in the rat brain using the in situ hybridization and immunohistochemical methods [3].
• In the presence of 1 mM reduced glutathione (GSH), the inactivated GST-P (-pi) was effectively reactivated by the action of thioltransferase, which had been partially purified from rat liver by GSH-Sepharose affinity chromatography and gel filtration using Sephadex G-75 [16].

References