Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P36969 (phospholipid hydroperoxide glutathione peroxidase)
 344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome c (cyt. c) is a proapoptotic factor that binds preferentially to cardiolipin (CL), a mitochondrial lipid, but not to cardiolipin hydroperoxide (CL-OOH). Cyt. c that had bound to CL liposomes was liberated on peroxidation of the liposomes by a radical. The generation of CL-OOH in mitochondria occurred before the release of cyt. c in rat basophile leukaemia (RBL)2H3 cells that had been induced to undergo apoptosis by exposure to hypoglycaemia with 2-deoxyglucose (2DG). The amount of cyt. c bound to CL prepared from the mitochondria of 2DG-treated cells was lower than that of untreated cells. The release of cyt. c was completely suppressed when the production of CL-OOH in mitochondria was inhibited by the overexpression of mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx). The fluorescence from CL-labelling dye (10-N-nonyl Acridine Orange) decreased on the induction of apoptosis by 2DG. However, no decrease in fluorescence was observed in PHGPx-overexpressing cells. Cyt. c was released from mitochondria that had been isolated from control cells on peroxidation by t-butylhydroperoxide, but no similar liberation of cyt. c from mitochondria isolated from mitochondrial PHGPx-overexpressing cells was observed. These findings suggest that the generation of CL-OOH in mitochondria might be a primary event that triggers the release of cyt. c from mitochondria in the apoptotic process in which mitochondrial PHGPx participates as an anti-apoptotic factor by preventing the formation of CL-OOH.
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PMID:Mitochondrial phospholipid hydroperoxide glutathione peroxidase inhibits the release of cytochrome c from mitochondria by suppressing the peroxidation of cardiolipin in hypoglycaemia-induced apoptosis. 1099 61

Overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in mitochondria of RBL2H3 cells (M15 cells) prevented the release of cytochrome c (cyt.c), the activation of caspase-3, and apoptosis caused by 2-deoxyglucose (2DG), whereas cells overexpressing nonmitochondrial PHGPx(L9) and control (S1) cells were induced to apoptosis. Hydro-peroxide levels in mitochondria of L9 and S1 cells were significantly enhanced by 2DG-induced apoptosis. In contrast, generation of hydroperoxide in mitochondria was protected in M15 cells, which also showed resistance to apoptosis by etoposide, staurosporine, UV irradiation, cycloheximide, and actinomycin D, stimuli that induce apoptosis by the liberation of cyt.c from mitochondria. Cyt.c preferentially binds to the monolayer of cardiolipin (CL), the specific phospholipid of the inner membrane of mitochondria. The amount of cyt.c bound to the monolayer of cardiolipin hydroperoxide (CL-OOH) was much lower than that bound to CL. Cyt.c bound to liposome containing CL was released by peroxidation with a radical initiator. Adenine nucleotide translocator (ANT), which regulates the opening and closing the permeability transition (PT) pore, potentially was inactivated in apoptosis-induced S1 cells 4 h after the addition of 2DG, coincidentally with cyt.c release from mitochondria. ANT activity was suppressed by the fusion of isolated mitochondria with liposomes containing CL-OOH. ANT activity was expressed in proteoliposomes containing 10% CL, but it was competitively inhibited by the addition of CL-OOH. This study suggests that CL peroxidation might have an initiating role in the liberation of cyt.c from the inner membrane, and in the opening of the PT pore via inactivation of ANT. Mitochondrial PHGPx might play a role as an anti-apoptotic factor by protecting CL and reducing CL-OOH.
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PMID:Initiation of apoptotic signal by the peroxidation of cardiolipin of mitochondria. 1512 95

One, 1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), the major metabolite of 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant (POPs) and male reproductive toxicant. However, the mechanism by which p,p'-DDE exposure causes male reproductive toxicity remains unknown. The objective of this study was to elucidate some mechanisms involved in this process, including the mitochondria apoptosis pathway and the role of phospholipid hydroperoxide glutathione peroxidase (PHGPx). Puberty male SD rats were given different doses of p,p'-DDE (0, 20, 60, 100 mg/kg body weight), after the treatment, the semen quality was evaluated. Western blotting was used to detect the PHGPx protein expression. Furthermore, real-time PCR was used to analyze the genetic expression of PHGPx, Bax, Cytochrom C (Cyt C), Apaf-1, and caspase-3 in the testis. Results indicated that after the exposure, sperm malformation rate showed a significant rise compared with the control group, and meanwhile, the sperm density and sperm motility parameters were reduced to some extent in different treated groups. The mitochondria apoptosis pathway was activated. And remarkably, the expression of PHGPx protein was greatly reduced by the exposure. We conclude that p,p'-DDE can damage spermatogenesis via PHGPx depletion and mitochondria apoptosis pathway.
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PMID:p,p'-DDE damages spermatogenesis via phospholipid hydroperoxide glutathione peroxidase depletion and mitochondria apoptosis pathway. 2541 Jul 18