Hypoxia induces apoptosis in human neuroblastoma SK-N-MC cells by caspase activation accompanying cytochrome c release from mitochondria

Runa Araya, Takashi Uehara, Yasuyuki Nomura

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

Abstract

We have attempted to elucidate the mechanism of apoptotic cell death induced by hypoxia (very low oxygen conditions) in neuronal cells. Human neuroblastoma SK-N-MC cells under hypoxic conditions resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay and nuclear morphology stained with fluorescent chromatin dye. Pretreatment with Z-Asp-CH2-DCB, a caspase inhibitor, suppressed the DNA ladder in response to hypoxia in a concentration-dependent manner. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. To confirm the involvement of caspase-3 during apoptosis, Western blot analysis was performed using anti-caspase-3 antibody. The 20- and 17-kDa proteins, corresponding to the active products of caspase-3, were generated in hypoxia-challenged lysates in which processing of the full length form of caspase-3 was evident. With a time course similar to this caspase-3 activation, hypoxic stress caused the cleavage of PARP, yielding an 85-kDa fragment typical of caspase activity. In addition, caspase-2 was also activated by hypoxia, and the stress elicited the release of cytochrome c into the cytosol during apoptosis. These results suggest that caspase activation and cytochrome c release play roles in hypoxia-induced neuronal apoptosis. Copyright (C) 1998 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)168-172
Number of pages5
JournalFEBS Letters
Volume439
Issue number1-2
DOIs
Publication statusPublished - Nov 13 1998
Externally publishedYes

Keywords

  • Apoptosis
  • Caspase
  • Cytochrome c
  • Hypoxia
  • Neuronal cell

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Hypoxia induces apoptosis in human neuroblastoma SK-N-MC cells by caspase activation accompanying cytochrome c release from mitochondria'. Together they form a unique fingerprint.

Cite this