Possible involvement of caspase activation in nitric oxide-induced neuronal apoptosis in SH-SY5Y cells

Takashi Uehara, Y. Nomura

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We here report involvement of caspases in NO-induced neuronal apoptosis. Our experiments were designed to elucidate how NO induces neuronal cell death using NOC18, a new type of NO donor that spontaneously releases NO alone, without enzymatic metabolization. NOC18 induced apoptosis in human neuroblastoma SH-SY5Y cells in a concentration- and time-dependent manner estimated with DNA fragmentation assay, FACScan analysis, and nuclear morphology. In this study, oxyhemoglobin, an NO trapper, suppressed NOC18-triggered DNA fragmentation, indicating that NO from NOC18 is an apoptosis-inducer. An increase in caspase-3-like protease activity was observed in parallel with the induction of apoptosis, but no caspase-1-like protease activity was detected. The level of pro-caspase-2 protein, a precursor of caspase-2, was decreased dramatically. In addition, NOC18 also caused the cleavage of PARP, yielding an 85 kDa protein, a typical fragment of the caspases reaction. Oxyhemoglobin blocked the decrease in pro-caspase-2 and the cleavage of PARP by NOC18. Moreover, NO elicited the release of cytochrome c into the cytosol from mitochondria during apoptosis. These results suggest that activation of caspases by cytochrome c released from mitochondria is involved in neuronal apoptosis induced by NO.

Original languageEnglish
JournalFolia Pharmacologica Japonica
Volume112 Suppl 1
Publication statusPublished - Oct 1998
Externally publishedYes

Fingerprint

Caspases
Nitric Oxide
Caspase 2
Apoptosis
Oxyhemoglobins
DNA Fragmentation
Cytochromes c
Mitochondria
Peptide Hydrolases
Caspase 1
Protein Precursors
Neuroblastoma
Caspase 3
Cytosol
Cell Death
Proteins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Possible involvement of caspase activation in nitric oxide-induced neuronal apoptosis in SH-SY5Y cells. / Uehara, Takashi; Nomura, Y.

In: Folia Pharmacologica Japonica, Vol. 112 Suppl 1, 10.1998.

Research output: Contribution to journalArticle

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