Nitric Oxide Inhibits Fas-induced Apoptosis

Mannick, Joan B.; Miao, Xiaoqing; Stamler, Jonathan S.

doi:10.1074/jbc.272.39.24125

Cited by 297 publications

(176 citation statements)

References 62 publications

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“…[90,91,91] Most studies suggest that the dominant anti-apoptotic effect of NO• in hepatocytes involves the direct modification of caspases by S-nitrosation. [28,37,40,75,92] Caspases are cysteine proteases, and all possess active-site cysteine residues essential for their activity. This cysteine is susceptible to S-nitrosation that blocks enzyme activity.…”

Section: Chemical Fate Of No• In Biological Systemsmentioning

confidence: 99%

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Vodovotz¹,

Kim²,

Bagci³

et al. 2004

CMM

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Section: Chemical Fate Of No• In Biological Systemsmentioning

confidence: 99%

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Vodovotz¹,

Kim²,

Bagci³

et al. 2004

CMM

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“…8 Nitric oxide, another reactive species, is also known to inhibit Fas mediated apoptosis. 9 Activation of cysteine death proteases, caspases, is required for commitment to Fas mediated apoptosis. 10 Recent studies have hypothesized that maintenance of a reducing environment inside the cell is necessary for caspase activity during apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Fas mediated apoptosis of human Jurkat T-cells: intracellular events and potentiation by redox-active α-lipoic acid

1999

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Activation of caspases is required in Fas receptor mediated apoptosis. Maintenance of a reducing environment inside the cell has been suggested to be necessary for caspase activity during apoptosis. We explored the possibility to potentiate Fas mediated killing of tumor cells by a-lipoic acid (LA), a redox-active drug and nutrient that is intracellularly reduced to a potent reductant dihydrolipoic acid. Treatment of cells with 100 mM LA for 72 h markedly potentiated Fas-mediated apoptosis of leukemic Jurkat cells but not that of peripheral blood lymphocytes from healthy humans. In Jurkat, Fas activation was followed by rapid loss of cell thiols, decreased mitochondrial membrane potential, increased [Ca 2+ ] i and increased PKC activity; all these responses were potentiated in LA pretreated cells. PKCd played an important role in mediating the effect of LA on Fas-mediated cell death. In response to Fas activation LA treatment potentiated caspase 3 activation by over 100%. The ability of LA to potentiate Fas mediated killing of leukemic cells was abrogated by a caspase 3 inhibitor suggesting that increased caspase 3 activity in LAtreated Fas-activated cells played an important role in potentiating cell death. This work provides first evidence showing that inducible caspase 3 activity may be pharmacologically up-regulated by reducing agents such as dihydrolipoic acid.

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“…Even basal levels of cGMP, generated primarily by basal sGC activity, and subsequent partial activation of PKG are sufficient (in fact, necessary) to prevent spontaneous apoptosis in certain cells, including NG108-15 cells (Fiscus, 2002;Fiscus et al, 2002), immortalised uterine epithelial cells (Chan and Fiscus, 2003), and human ovarian cancer cells (Fraser et al, 2006). Because sGC is activated by NO at very low concentrations (i.e., 50% of maximal NO;Bellamy et al, 2002), low endogenous level of NO, generated by one of the three NOSs, may be responsible for stimulating basal sGC activity and inhibiting apoptosis in these cells.Previously, melanoma cells (Tang and Grimm, 2004), transformed b-cell line RINm5F (Tejedo et al, 2001), and transformed human leukocytes (Mannick et al, 1997) were reported to generate endogenous NO capable of suppressing apoptosis. Endogenous NO is also believed to be responsible for aggressive tumour progression, metastasis, and poor survival in cancer patients with tumours exhibiting increased iNOS expression (Thomsen and Miles, 1998).…”

mentioning

confidence: 99%

“…Previously, melanoma cells (Tang and Grimm, 2004), transformed b-cell line RINm5F (Tejedo et al, 2001), and transformed human leukocytes (Mannick et al, 1997) were reported to generate endogenous NO capable of suppressing apoptosis. Endogenous NO is also believed to be responsible for aggressive tumour progression, metastasis, and poor survival in cancer patients with tumours exhibiting increased iNOS expression (Thomsen and Miles, 1998).…”

mentioning

confidence: 99%

Cisplatin alters nitric oxide synthase levels in human ovarian cancer cells: involvement in p53 regulation and cisplatin resistance

et al. 2008

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The present study determines if (1) basal protein levels of nitric oxide (NO) synthases (eNOS, iNOS, and nNOS) are different in cisplatin-sensitive (OV2008) and counterpart cisplatin-resistant (C13*) human ovarian cancer cells, (2) cisplatin alters NOS levels, (3) NO donor causes apoptosis and p53 upregulation, (4) NO donor sensitises C13* cells to cisplatin via p53 upregulation (determined by p53 siRNA gene-knockdown), and (5) inhibition of endogenous NOS alters cisplatin-induced apoptosis. Basal iNOS levels were higher in OV2008 cells than in C13* cells. Cisplatin upregulated iNOS, but dramatically reduced eNOS and nNOS, in OV2008 cells only. Failure of cisplatin to upregulate iNOS and downregulate eNOS/nNOS in cisplatin-resistant C13* cells may be an aetiological factor in the development of resistance. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) increased p53 protein levels and induced apoptosis in both cell types, and enhanced cisplatin-induced apoptosis in C13* cells in a p53-dependent manner (i.e., enhancement blocked by p53 siRNA). Specific iNOS inhibitor 1400W partially blocked cisplatin-induced apoptosis in OV2008 cells. In cisplatin-resistant C13* cells, blocking all NOSs with N G -amino-L-arginine dramatically changed these cells from cisplatin-resistant to cisplatin-sensitive, greatly potentiating cisplatin-induced apoptosis. The data suggest important roles for the three NOSs in regulating chemoresistance to cisplatin in ovarian cancer cells. (Siddik, 2003), and the induction of apoptosis is a key determinant of CDDP sensitivity. Indeed, we and others have demonstrated that failure of CDDP to induce apoptosis is a major component of CDDP resistance (Sasaki et al, 2000;Yuan et al, 2003;Fraser et al, 2003a). CDDP induces DNA crosslinks, upregulation of p53, and subsequent p53-dependent apoptosis (Siddik, 2003). However, in CDDP-resistant ovarian cancer cells, failure to properly regulate p53 can contribute to the resistance (Fraser et al, 2003a, b). Furthermore, basal activity of soluble guanylyl cyclase (sGC), an intracellular receptor for nitric oxide (NO), suppresses apoptosis in ovarian cancer cells, partly via inhibition of p53 accumulation and activation (Fraser et al, 2006). We hypothesised that basal sGC activity and regulation of p53 may depend on endogenous NO formed by one of the three NO synthases (NOSs), eNOS (also called NOS3), iNOS (also called NOS2), or nNOS (also called NOS1) and that resistance to CDDP in ovarian cancer cells may involve altered expression of the NOSs.At high concentrations (typically 4100 mM), NO donors generate toxic concentrations of NO (e.g., 4100 nM), inducing apoptosis in many mammalian cells (Fiscus, 2002;Fiscus et al, 2002), including cancer cells (Wink et al, 1998). However, NO at lower, more physiological levels (e.g., 1 -20 nM) often has the opposite effect, preventing (or attenuating) the onset of apoptosis in many mammalian cells, including lung fibroblasts (Wink et al, 1993), human B lymphocytes (Mannick et al, 1994), and many normal and trans...

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Nitric Oxide Inhibits Fas-induced Apoptosis

Cited by 297 publications

References 62 publications

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Fas mediated apoptosis of human Jurkat T-cells: intracellular events and potentiation by redox-active α-lipoic acid

Cisplatin alters nitric oxide synthase levels in human ovarian cancer cells: involvement in p53 regulation and cisplatin resistance

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