Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, tamoxifen (TAM) has been shown to induce apoptosis through elevation of intracellular Ca2+ in HepG2 human hepatoblastoma cells. In this study we investigated the role of reactive oxygen species (ROS) in the TAM-induced apoptosis, and interrelationship between intracellular Ca2+ and ROS. TAM induced a slow and sustained increase in intracellular ROS level. An antioxidant, N-acetylcysteine significantly inhibited both ROS production and apoptosis induced by TAM, suggesting that ROS may play an essential role in the TAM-induced apoptosis. In a time frame ROS generation followed intracellular Ca2+ increase, and the extracellular and intracellular Ca2+ chelation with EGTA and BAPTA/AM, respectively, completely inhibited the TAM-induced ROS production, indicating that intracellular Ca2+ may mediate the ROS generation. Inhibitors of NAD(P)H oxidase, diphenylene iodonium, phenylarsine oxide and neopterine, significantly blocked the TAM-induced ROS generation and apoptosis, implying that this oxidase may act as a source enzyme for the production of ROS. These results suggest that non-phagocytic NAD(P)H oxidase may play a novel role as a mediator of the apoptosis associated with intracellular Ca2+ in HepG2 cells.
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PMID:Role of NAD(P)H oxidase in the tamoxifen-induced generation of reactive oxygen species and apoptosis in HepG2 human hepatoblastoma cells. 1127 38

K(+)-Cl(-)-cotransport (KCC) is ubiquitously present in all cells, and plays an essential role in ion and volume regulation. In this study we investigated the role of reactive oxygen species (ROS) in regulation of KCC in HepG2 human hepatoblastoma cells. N-ethylmaleimide (NEM), a KCC activator, induced Cl(-)-dependent K+ efflux, which was markedly prevented by KCC inhibitors (calyculin-A, genistein and BaCl2), indicating that KCC is activated by NEM in the HepG2 cells. Treatment with NEM also induced a sustained increase in the level of intracellular ROS assessed by 2',7'-dichlorofluorescein fluorescence. Antioxidants, N-acetyl cysteine or N,N'-diphenyl-p-phenylenediamine significantly inhibited both ROS generation and KCC activation induced by NEM. The NEM-induced ROS production was significantly suppressed by inhibitors of NADPH oxidase (diphenylene iodonium, apocynin and neopterine). These inhibitors also significantly inhibited the NEM-induced KCC activation. Taken together, these results suggest that ROS generated by NADPH oxidase may mediate the NEM-induced activation of KCC in human hepatoma cells.
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PMID:Role of reactive oxygen species generated by NADPH oxidase in the mechanism of activation of K(+)-Cl(-)-cotransport by N-ethylmaleimide in HepG2 human hepatoma cells. 1169 16

We have previously reported that N-ethylmaleimide induces apoptosis through activation of K(+), Cl(-)-cotransport in HepG2 human hepatoblastoma cells. In this study, we investigated the role for reactive oxygen species as a mediator of the apoptosis induced by N-ethylmaleimide. N-ethylmaleimide induced a significant elevation of intracellular level of reactive oxygen species. Treatment with antioxidants (N-acetyl cysteine, N,N'-diphenyl-p-phenylenediamine) which markedly suppressed generation of reactive oxygen species, significantly inhibited the N-ethylmaleimide-induced activation of K(+), Cl(-)-cotransport and apoptosis. Inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, D-(+)-neopterine) also significantly blunted the generation of reactive oxygen species, activation of K(+), Cl(-)-cotransport and apoptosis induced by N-ethylmaleimide. These results suggest that reactive oxygen species generated through activation of NADPH oxidase may play a role in the N-ethylmaleimide-induced stimulation of K(+), Cl(-)-cotransport and apoptosis in HepG2 cells.
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PMID:Role of reactive oxygen species in apoptosis induced by N-ethylmaleimide in HepG2 human hepatoblastoma cells. 1175 28

Although capsaicin (8-methyl-N-vanillyl-6-nonenamide), a pungent ingredient in a variety of red peppers of the genus Capsicum, has been shown to induce apoptotic cell death in many cancer cells, the exact mechanism of this action of capsaicin is not completely understood. In this study, we investigated the possible mediation of the NADPH oxidase-modulated production of reactive oxygen species (ROS) in the apoptotic mechanism of capsaicin in HepG2 human hepatoblastoma cells. Capsaicin induced apoptotic cell death in a time- and dose-dependent manner. Capsaicin at the concentration of inducing apoptosis also markedly increased the level of ROS. The capsaicin-induced generation of ROS and apoptosis was significantly suppressed by treatment with antioxidants, DPPD and tocopherol. In addition, inhibitors of NADPH oxidase, diphenylene iodonium, apocynin and neopterine, profoundly blocked the capsaicin-induced ROS generation and apoptosis. The expression of Rac1N17, a dominant negative mutant of Rac1, also significantly inhibited the capsaicin-induced apoptosis. Activation of nuclear factor-kappaB, a transcription factor essentially involved in ROS-induced apoptosis, was also observed by treatment with capsaicin. Collectively, these results suggest that the NADPH oxidase-mediated generation of ROS may be essentially involved in the mechanism of capsaicin-induced apoptosis in HepG2 cells. These results further suggest that capsaicin may be a valuable agent for the therapeutic intervention of human hepatomas.
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PMID:Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apototic cell death by capsaicin in HepG2 human hepatoma cells. 1519 Sep 37