Nitric Oxide-Mediated Apoptosis in Murine Mastocytoma

Kitajima, Isao; Kikuchi, Kôichi; Nakajima, Takeshi; Soejima, Yasuko; Matsuyama, Tomohiko; Maruyama, Ikuro

doi:10.1006/bbrc.1994.2451

Cited by 68 publications

(29 citation statements)

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“…This observation added to existing evidence that NO is an important regulator of MC activity, modulating cell survival, mediator secretion, and gene expression (11)(12)(13)(14)(15). The ability of NO to act as a potent down-regulator of multiple MC functions suggests that it is impinging upon one or more crucial signaling pathways in the cell.…”

Section: Ast Cells (Mc)mentioning

confidence: 77%

Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion

Forsythe

Befus

2003

The Journal of Immunology

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Nitric oxide is an important messenger that regulates mast cell activity by modifications to gene expression and intracellular pathways associated with exocytosis and adhesion. Integrin interactions with extracellular matrix components modulate an array of cell activities, including mediator production and secretion. To investigate the molecular mechanisms underlying NO regulation of mast cell function, we studied its effects on adhesion of a human mast cell line (HMC-1) to fibronectin (FN). The NO donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine strongly down-regulated the adhesion of HMC-1 to FN. Inhibitors of soluble guanylate cyclase and protein kinase G did not alter the response of cells to NO. A peroxynitrite scavenger did not affect modulation of adhesion by NO, nor could the effect of NO be mimicked by the peroxynitrite-producing compound 3-morpholinosydnonimine. NO donors inhibited the cysteine protease, calpain, while calpain inhibitors mimicked the effect of NO and led to a decrease in the ability of HMC-1 cells to adhere to FN. Thus, NO is an effective down-regulator of human mast cell adhesion. The mechanism for this action does not involve peroxynitrite or activation of soluble guanylate cyclase. Instead, a portion of NO-induced down-regulation of adhesion may be attributed to inhibition of the cysteine protease, calpain, an enzyme that has been associated with control of integrin activation in other cell types. The inhibition of calpain is most likely mediated via nitrosylation of its active site thiol group. Calpain may represent a novel therapeutic target for the regulation of mast cell activity in inflammatory disorders.

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Section: Ast Cells (Mc)mentioning

confidence: 77%

Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion

Forsythe

Befus

2003

The Journal of Immunology

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“…The induction of apoptosis by NO is more likely the result of direct DNA damage as demonstrated by Nguyen et al (Nguyen et al, 1992). In addition, NO plays an important role in chemopreventive agents inducing cell apoptosis in previous studies (Kitajima et al, 1994;Ankarcrona et al, 1994;Kaneto et al, 1995;Zhang and Huang, 2005;Machiavelli et al, 2007). Therefore, it is reasonable to deduce that NO played a crucial role in PBDE-47 and HBCDs individually inducing cell apoptosis.…”

Section: Discussionmentioning

confidence: 90%

Effects of tetrabrominated diphenyl ether and hexabromocyclododecanes in single and complex exposure to hepatoma HepG2 cells

2009

Environmental Toxicology and Pharmacology

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“…Additionally, mouse MC undergoing apoptosis are dependent on endogenous NO signals, as NOS inhibitors prevented apoptosis from occurring (Kitajima et al 1994). …”

Section: Regulation Of Gtp-chi Expression Modulates Bhmentioning

confidence: 99%

“…NO can regulate autocrine apoptotic signals (Kitajima et al 1994), and alter surface molecule expression, namely CD8 (Nohara et al 2001). It is apparent that NO is important in both allergic and non-allergic functions of MC.…”

mentioning

confidence: 99%