The Nitric Oxide Donor NOC12 Protects Cultured Astrocytes Against Apoptosis via a cGMP-Depentent Mechanism

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Author(s)

Abstract

We examined the effect of 3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC12), a nitric oxide (NO) donor, on apoptosis in cultured astrocytes. Reperfusion after hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) exposure caused a decrease in cell viability, loss of mitochondrial membrane potential, caspase-3 activation, DNA ladder formation, and nuclear condensation. NOC12 at 10 – 100 μM significantly attenuated these apoptotic changes, while the NO donor at 1 mM caused cell injury and exacerbated the H<sub>2</sub>O<sub>2</sub>-induced cell injury. NOC12 increased intracellular cGMP levels in a dose dependent manner with the maximal effect at 100 μM. The protective effect of NOC12 was mimicked by the NO-independent guanylate cyclase activator 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole, and was attenuated by the guanylate cyclase inhibitor 1<i>H</i>-[1,2,4]oxadiazolo[4,3-<i>a</i>]quinoxalin-1-one (ODQ) and the cGMP-dependent protein kinase inhibitor KT5823. ODQ and KT5823 did not block but rather exacerbated the cytotoxic effect of NOC12 at 1 mM. These findings demonstrate that lower concentrations of NOC12 inhibit the H<sub>2</sub>O<sub>2</sub>-induced apoptosis of astrocytes in a cGMP-dependent way, but higher concentrations of NOC12 show a toxic effect on astrocytes in a cGMP-independent way.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 89(1), 64-71, 2002-05-01

    The Japanese Pharmacological Society

References:  40

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008431063
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    6170938
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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