Partial correction of abnormal cardiac development in caspase-8-deficient mice by cardiomyocyte expression of p 35.
Baculovirus p 35 protein protects cells from apoptotic cell death by inhibiting caspase activation. We have established transgenic mouse lines specifically expressing p 35 in cardiomyocytes, and primary cardiomyocytes isolated from these mice exhibit resistance to staurosporine-induced apoptosis. In a previous study, we observed defects in heart formation associated with abdominal hemorrhage and cardiomyocyte cell death in caspase-8-deficient animals. In order to better understand the etiology of the cardiac defects and embryonic lethality in caspase-8-deficient mice, we crossed these mice with the p 35 transgenic animals. Although the newly generated mice still died in utero and exhibited some cardiac defects, cardiomyocyte apoptosis was suppressed and ventricular trabeculation was restored. Thus, cardiomyocyte expression of p 35 prevented cell death induced by staurosporine or caspase-8 deficiency. Additionally, our data suggest that caspase-8 plays multiple roles in cardiac development.
Yajima
Nobuyuki
N
Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Yamada
Shu-Ichi
S
Morisaki
Takayuki
T
Toyokuni
Shinya
S
Yonehara
Shin
S
Sakamaki
Kazuhiro
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D053181:Caspase 8; D061945:Caspase Inhibitors; D020169:Caspases / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D004274:DNA, Recombinant / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006330:Heart Defects, Congenital / Q000196:embryology / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011247:Pregnancy; D011994:Recombinant Proteins / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics*
D061945:Caspase Inhibitors; D004274:DNA, Recombinant; D011994:Recombinant Proteins; D014764:Viral Proteins; C485184:enhanced green fluorescent protein; C492234:p35 protein, Baculovirus; D049452:Green Fluorescent Proteins; C505530:CASP8 protein, human; C505526:Casp8 protein, mouse; D053181:Caspase 8; D020169:Caspases; D019311:Staurosporine