Staurosporine-induced cleavage of α-smooth muscle actin during myofibroblast apoptosis

Ayako Nakazono-Kusaba, Fumi Takahashi-Yanaga, Sachio Morimoto, Masutaka Furue, Toshiyuki Sasaguri

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16 Citations (Scopus)

Abstract

To examine the possibility that staurosporine is applicable for the treatment of abnormal scar formation such as hypertrophic scar and keloid, the cellular process during staurosporine-induced apoptosis was analyzed in myofibroblasts isolated from a rat granulation tissue pouch. Staurosporine induced myofibroblast apoptosis in a time- and dose-dependent manner with typical morphologic changes. Staurosporine (1 μM) activated caspase-3 up to 3.6-fold by cleaving pro-caspase-3 (32 kDa) to active forms (17, 19, and 20 kDa). Microfilaments mainly composed of α-smooth muscle actin, a contractile protein characterizing myofibroblasts, were degraded during staurosporine-induced apoptosis. The degradation of α-smooth muscle actin bundles was detected as early as 1 h after the treatment with staurosporine. Recombinant active caspase-3 and staurosporine-stimulated caspase-3 both cleaved purified α-smooth muscle actin in vitro. These results suggested that α-smooth muscle actin is directly degraded by caspase-3 in response to apoptotic stimuli in myofibroblasts. In addition, bleomycin (100 ng per ml) and cisplatin (1 mM) also induced myofibroblast apoptosis by activating caspase-3, suggesting that these agents have a potential therapeutic value for abnormal scar formation.

Original languageEnglish
Pages (from-to)1008-1013
Number of pages6
JournalJournal of Investigative Dermatology
Volume119
Issue number5
DOIs
Publication statusPublished - 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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