Reperfusion, not simulated ischemia, initiates intrinsic apoptosis injury in chick cardiomyocytes.

Abstract

Although ischemia-reperfusion (I/R) can initiate apoptosis, the timing and contribution of the mitochondrial/cytochrome c apoptosis death pathway to I/R injury is unclear. We studied the timing of cytochrome c release during I/R and whether subsequent caspase activation contributes to reperfusion injury in confluent chick cardiomyocytes. One-hour simulated ischemia followed by 3-h reperfusion resulted in significant cell death, with most cell death evident during the reperfusion phase and demonstrating mitochondrial cytochrome c release within 5 min after reperfusion. By contrast, cells exposed to prolonged ischemia for 4 h had only marginally increased cell death and no detectable cytochrome c release into the cytosol. Caspase activation could not be detected after ischemia only, but it significantly increased after reperfusion. Caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, Ac-Asp-Gln-Thr-Asp-H, or benzyloxycarbonyl-Leu-Glu (Ome)-His-Asp-(Ome)-fluoromethyl ketone given only at reperfusion significantly attenuated cell death and resulted in return of contraction. Antixoxidants decreased cytochrome c release, nuclear condensation, and cell death. These results suggest that reperfusion oxidants initiate cytochrome c release within minutes, and apoptosis within hours, significant enough to increase cell death and contractile dysfunction.

• Authors: Terry L Vanden Hoek, Yimin Qin, Kim Wojcik, Chang-Qing Li, Zuo-Hui Shao, Travis Anderson, Lance B Becker, Kimm J Hamann
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 284 Issue 1 Pg. H141-50 (Jan 2003) ISSN: 0363-6135 [Print] United States
• PMID: 12388298 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antioxidants
• Carrier Proteins
• Cytochrome c Group
• Enzyme Inhibitors
• Microfilament Proteins
• fodrin
• Caspase 3
• Caspase 9
• Caspases

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects, physiology)
• Carrier Proteins (chemistry, metabolism)
• Caspase 3
• Caspase 9
• Caspases (metabolism)
• Cell Death (drug effects)
• Cell Nucleus (ultrastructure)
• Cells, Cultured
• Chick Embryo
• Cytochrome c Group (metabolism)
• Enzyme Activation
• Enzyme Inhibitors (pharmacology)
• Heart (physiopathology)
• Ischemia (physiopathology)
• Microfilament Proteins (chemistry, metabolism)
• Muscle Cells (physiology)
• Myocardium (pathology, ultrastructure)
• Reperfusion Injury (physiopathology)
• Time Factors