TY - JOUR
T1 - H9c2 cardiac myoblasts undergo apoptosis in a model of ischemia consisting of serum deprivation and hypoxia
T2 - Inhibition by PMA
AU - Bonavita, Francesca
AU - Stefanelli, Claudio
AU - Giordano, Emanuele
AU - Columbaro, Marta
AU - Facchini, Annalisa
AU - Bonafè, Francesca
AU - Caldarera, Claudio Marcello
AU - Guarnieri, Carlo
PY - 2003/2/11
Y1 - 2003/2/11
N2 - Cardiac myocytes undergo apoptosis under condition of ischemia. Little is known, however, about the molecular pathways that mediate this response. We show that serum deprivation and hypoxia, components of ischemia in vivo, resulted in apoptosis of rat ventricular myoblast cells H9c2. Hypoxia alone did not induce significant apoptosis for at least 48 h, but largely increased the proapoptotic action of serum deprivation. H9c2 cells apoptosis is evidenced by an increase in terminal (TdT)-mediated dUTP nick end-labeling-positive nuclei and by activation of caspases 3, 6, 7 and 9, and loss of mitochondrial functions. In this model of simulated ischemia, represented by serum deprivation plus hypoxia, cardiomyoblasts apoptosis was associated with a p53-independent Bax accumulation and with a down-regulation of Bcl-xL, whereas the levels of cIAP-1, cIAP-2 and X-IAP proteins did not change. Phorbol-12-myristate-13-acetate significantly reduced the induction of apoptosis, inhibiting caspase 3 cleavage, Bax accumulation, Bcl-xL down-regulation as well as restoring cell viability.
AB - Cardiac myocytes undergo apoptosis under condition of ischemia. Little is known, however, about the molecular pathways that mediate this response. We show that serum deprivation and hypoxia, components of ischemia in vivo, resulted in apoptosis of rat ventricular myoblast cells H9c2. Hypoxia alone did not induce significant apoptosis for at least 48 h, but largely increased the proapoptotic action of serum deprivation. H9c2 cells apoptosis is evidenced by an increase in terminal (TdT)-mediated dUTP nick end-labeling-positive nuclei and by activation of caspases 3, 6, 7 and 9, and loss of mitochondrial functions. In this model of simulated ischemia, represented by serum deprivation plus hypoxia, cardiomyoblasts apoptosis was associated with a p53-independent Bax accumulation and with a down-regulation of Bcl-xL, whereas the levels of cIAP-1, cIAP-2 and X-IAP proteins did not change. Phorbol-12-myristate-13-acetate significantly reduced the induction of apoptosis, inhibiting caspase 3 cleavage, Bax accumulation, Bcl-xL down-regulation as well as restoring cell viability.
KW - Apoptosis
KW - Bcl-2 family proteins
KW - Caspase
KW - H9c2
KW - Ischemia
KW - Phorbol-12-myristate-13-acetate
UR - http://www.scopus.com/inward/record.url?scp=0037432170&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037432170&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(03)00029-2
DO - 10.1016/S0014-5793(03)00029-2
M3 - Article
C2 - 12586343
AN - SCOPUS:0037432170
VL - 536
SP - 85
EP - 91
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1-3
ER -