scholarly journals PEGylation and antioxidant effects of a human glutathione peroxidase 1 mutant

Aging ◽  
2022 ◽  
Author(s):  
Guang-Yuan Zhang ◽  
Yan-Wei Wang ◽  
Li-Ying Guo ◽  
Liang-Ru Lin ◽  
Shao-Peng Niu ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Glutathione Peroxidase 1 ◽  
Antioxidant Effects

scholarly journals Glutathione peroxidase-1 regulates ASK1-dependent apoptosis via interaction with TRAF2 in RIPK3-negative cancer cells

2021 ◽  
Author(s):  
Sunmi Lee ◽  
Eun-Kyung Lee ◽  
Dong Hoon Kang ◽  
Jiyoung Lee ◽  
Soo Hyun Hong ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Cancer Cells ◽  
Mammalian Cells ◽  
Apoptosis Pathway ◽  
Glutathione Peroxidase 1 ◽  
Peroxidase Enzyme ◽  
Thioredoxin 1 ◽  
Sequential Activation ◽  
Induced Apoptosis

AbstractGlutathione peroxidase (GPx) is a selenocysteine-containing peroxidase enzyme that defends mammalian cells against oxidative stress, but the role of GPx signaling is poorly characterized. Here, we show that GPx type 1 (GPx1) plays a key regulatory role in the apoptosis signaling pathway. The absence of GPx1 augmented TNF-α-induced apoptosis in various RIPK3-negative cancer cells by markedly elevating the level of cytosolic H2O2, which is derived from mitochondria. At the molecular level, the absence of GPx1 led to the strengthened sequential activation of sustained JNK and caspase-8 expression. Two signaling mechanisms are involved in the GPx1-dependent regulation of the apoptosis pathway: (1) GPx1 regulates the level of cytosolic H2O2 that oxidizes the redox protein thioredoxin 1, blocking ASK1 activation, and (2) GPx1 interacts with TRAF2 and interferes with the formation of the active ASK1 complex. Inducible knockdown of GPx1 expression impaired the tumorigenic growth of MDA-MB-231 cells (>70% reduction, P = 0.0034) implanted in mice by promoting apoptosis in vivo. Overall, this study reveals the apoptosis-related signaling function of a GPx family enzyme highly conserved in aerobic organisms.

LOSS OF GLUTATHIONE PEROXIDASE 1 ATTENUATES COLITIS AND IS CRITICAL IN ACTIVATING EPITHELIAL REGENERATIVE RESPONSES

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S27-S27
Author(s):  
Jared Hendren ◽  
Koral Kasnyik ◽  
Christopher Williams ◽  
Sarah Short
Keyword(s):  
Stem Cell ◽  
Glutathione Peroxidase ◽  
Target Genes ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Cellular Metabolism ◽  
Intestinal Injury ◽  
Gene Set Enrichment Analysis ◽  
Intestinal Cell ◽  
Glutathione Peroxidase 1

Abstract Many selenium-containing “selenoproteins” function as antioxidants, and work by our lab and others has demonstrated that selenoproteins often protect against intestinal inflammatory diseases, including colitis. Glutathione peroxidase 1 (GPx1) is a ubiquitous, mitochondrial and cytosolic selenoprotein which catalyzes the reduction of hydrogen peroxide by glutathione. Previously, we determined that despite its antioxidant role, loss of GPx1 greatly reduced disease severity in the dextran sodium sulfate (DSS) colitis model. Furthermore, GPx1 loss increased baseline intestinal cell proliferation, enhanced enteroid plating efficiency, and induced expression of stem cell-associated genes, such as Lgr5. Next, we aimed to determine the mechanism by which GPx1 modifies response to DSS. We observed that GPx1 is increased in colonic tissues from DSS-treated mice as compared to nontreated controls, suggesting that GPx1 may functionally contribute to intestinal injury responses. While GPx1 is expressed in both intestinal epithelial and immune cells, in situ hybridization to visualize Gpx1 identified epithelial cells as the most highly expressing cell type, with the greatest Gpx1 upregulation observed in wound-adjacent and regenerative crypts. Next, we investigated whether GPx1 loss affects stem cell function after injury. Here, we determined that both proliferation (p<0.01) and Lgr5 expression (p<0.05) were increased in the crypts of Gpx1-/- DSS-treated mice in comparison to WT controls. Similarly, organoids established from ulcerative colitis tissue displayed increased growth rates (p<0.01), expression of stem cell and Wnt target genes such as AXIN2 (p<0.0001) and LGR5 (p<0.01), and proliferation (p<0.05) following GPX1 knockdown. Together, these results indicate that GPx1 has an epithelial-cell autonomous role, and that its loss activates stem cell and proliferative responses which may both protect from intestinal injury and promote healing. Interestingly, recent research has highlighted the role of cellular metabolism in maintaining intestinal stem cell function, and GPx1 has previously been implicated in these processes. RNA-sequencing from DSS-treated mice and gene set enrichment analysis identified a positive association with oxidative phosphorylation-associated genes in Gpx1-/- mice (NES: 1.78; FDR q-val: 0.01), suggesting altered metabolism which may favor stem cell function. Further analysis of cellular metabolism using GPX1 knockdown colorectal cancer cells observed higher basal respiration (p<0.0001) and ATP generation (p<0.0001). Together, these results suggest that unlike other intestinal selenoproteins studied to date, loss of GPx1 augments stem cell injury responses to protect against intestinal inflammation, likely via augmenting epithelial regenerative responses.

THE ROLE OF GLUTATHIONE PEROXIDASE 1 CODON 198 (GPX1 Pro198Leu) POLYMORPHISM IN PATIENTS WITH PROSTATE CANCER

2008 ◽  
Vol 179 (4S) ◽  
pp. 459-459
Author(s):  
Canan Kucukgergin ◽  
Oner Sanli ◽  
Tzevat Tefik ◽  
Ismet Nane ◽  
Sule Seckin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glutathione Peroxidase ◽  
Glutathione Peroxidase 1

scholarly journals Nox1 causes ileocolitis in mice deficient in glutathione peroxidase-1 and -2

2014 ◽  
Vol 68 ◽  
pp. 315-325 ◽  
Author(s):  
Robert S. Esworthy ◽  
Byung-Wook Kim ◽  
Joni Chow ◽  
Binghui Shen ◽  
James H. Doroshow ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Glutathione Peroxidase 1

scholarly journals Aminoglycosides Decrease Glutathione Peroxidase-1 Activity by Interfering with Selenocysteine Incorporation

2005 ◽  
Vol 281 (6) ◽  
pp. 3382-3388 ◽  
Author(s):  
Diane E. Handy ◽  
Gaozhen Hang ◽  
John Scolaro ◽  
Nicole Metes ◽  
Nadia Razaq ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Glutathione Peroxidase 1

Sa129 LOSS OF GLUTATHIONE PEROXIDASE 1 ATTENUATES COLITIS AND ACTIVATES EPITHELIAL REGENERATIVE RESPONSES

2021 ◽  
Vol 160 (6) ◽  
pp. S-431
Author(s):  
Jared R. Hendren ◽  
Koral M. Kasnyik ◽  
Mary K. Washington ◽  
Christopher S. Williams ◽  
Sarah P. Short
Keyword(s):  
Glutathione Peroxidase ◽  
Glutathione Peroxidase 1

LOSS OF GLUTATHIONE PEROXIDASE 1 ATTENUATES COLITIS AND IS CRITICAL IN ACTIVATING EPITHELIAL REGENERATIVE RESPONSES

2021 ◽  
Vol 160 (3) ◽  
pp. S35
Author(s):  
Jared Hendren ◽  
Koral Kasnyik ◽  
Christopher Williams ◽  
Sarah Short
Keyword(s):  
Glutathione Peroxidase ◽  
Glutathione Peroxidase 1
Sign in / Sign up

Export Citation Format

Share Document