title: Staurosporine-induced cleavage of alpha-smooth muscle actin during myofibroblast apoptosis.
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 microM) 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 alpha-smooth muscle actin, a contractile protein characterizing myofibroblasts, were degraded during staurosporine-induced apoptosis. The degradation of alpha-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 alpha-smooth muscle actin in vitro. These results suggested that alpha-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.
authors.affiliation: Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakazono-Kusaba
authors.forename: Fumi
authors.initials: F
authors.lastname: Takahashi-Yanaga
authors.forename: Sachio
authors.initials: S
authors.lastname: Morimoto
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasaguri
mesh_terms: D000199:Actins / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002921:Cicatrix / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006097:Granulation Tissue / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine