The Mitochondrial Apoptotic Pathway Is Activated by Serum and Glucose Deprivation in Cardiac Myocytes

Many cell types undergo apoptosis under conditions of ischemia. Little is known, however, about the molecular pathways that mediate this response. A cellular and biochemical approach to elucidate such signaling pathways was undertaken in primary cultures of cardiac myocytes, a cell type that is espe...

Full description

Saved in:

Bibliographic Details
Published in:	Circulation research 1999-09, Vol.85 (5), p.403-414
Main Authors:	Bialik, Shani, Cryns, Vincent L, Drincic, Andjela, Miyata, Setsuya, Wollowick, Adam L, Srinivasan, Anu, Kitsis, Richard N
Format:	Article
Language:	eng
Subjects:	Amino Acid Chloromethyl Ketones - pharmacology Animals Animals, Newborn Apoptosis - drug effects Apoptosis - physiology Biological and medical sciences Biomarkers Blood Physiological Phenomena Cardiology. Vascular system Caspase 3 Caspase 9 Caspase Inhibitors Caspases - physiology Cells, Cultured Coronary heart disease Culture Media - pharmacology Cysteine Proteinase Inhibitors - pharmacology Cytochrome c Group - analysis Glucose - pharmacology Heart Medical sciences Membrane Potentials Mitochondria, Heart - physiology Muscle Proteins - antagonists & inhibitors Muscle Proteins - physiology Myocardial Ischemia - pathology Myocardium - cytology Oxidoreductases - analysis Rats Signal Transduction - physiology
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Many cell types undergo apoptosis under conditions of ischemia. Little is known, however, about the molecular pathways that mediate this response. A cellular and biochemical approach to elucidate such signaling pathways was undertaken in primary cultures of cardiac myocytes, a cell type that is especially sensitive to ischemia-induced apoptosis. Deprivation of serum and glucose, components of ischemia in vivo, resulted in myocyte apoptosis, as determined by nuclear fragmentation, internucleosomal cleavage of DNA, and processing of caspase substrates. These manifestations of apoptosis were blocked by zVAD-fmk, a peptide caspase inhibitor, indicating that caspase activity is necessary for the progression of apoptosis in this model. In contrast to control cells, apoptotic myocytes exhibited cytoplasmic accumulation of cytochrome c, indicating release from the mitochondria. Furthermore, both caspase-9 and caspase-3 were processed to their active forms in serum-/glucose-deprived myocytes. Caspase processing, but not cytochrome c release, was inhibited by zVAD-fmk, placing the latter event upstream of caspase activation. This evidence demonstrates that components of ischemia activate the mitochondrial death pathway in cardiac myocytes.
ISSN:	0009-7330 1524-4571