TY - JOUR
T1 - Staurosporine-induced cleavage of α-smooth muscle actin during myofibroblast apoptosis
AU - Nakazono-Kusaba, Ayako
AU - Takahashi-Yanaga, Fumi
AU - Morimoto, Sachio
AU - Furue, Masutaka
AU - Sasaguri, Toshiyuki
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1046/j.1523-1747.2002.19525.x
DO - 10.1046/j.1523-1747.2002.19525.x
M3 - Article
C2 - 12445185
AN - SCOPUS:0036446758
VL - 119
SP - 1008
EP - 1013
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 5
ER -