Second window of ischemic preconditioning regulates mitochondrial permeability transition pore by enhancing Bcl-2 expression.
OBJECTIVE
The second window of protection (SWOP) following brief coronary artery occlusion begins at 24 h and may last up to 72 h and occurs via many unknown mechanisms. We investigated the role of the mitochondrial permeability transition pore (PTP), a non specific pore in the inner membrane of the mitochondria in this phenomenon.


METHODS
Ischemic preconditioning (IP) was induced in Wistar rats by left coronary artery occlusion (four, 3-min episodes separated by 10 min of reperfusion) on day 1. On day 2, ischemia was induced with 30 min of ischemia and 120 min of reperfusion in IP and control rats.


RESULTS
IP rats showed decreased myocardial infarction (MI) area vs. non-IP control rats (15.32 vs. 45.6%). Furthermore, IP rats had preserved cardiac function (heart rate, rate pressure product, coronary flow and aortic flow) and myocardial ATP (P<0.03), decreased tissue water content (73.2 vs. 90.6%), increased expression of Bcl-2, and less mitochondrial swelling, cytochrome C release and apoptosis (2.6 vs. 12.4%) when compared to sham-operated rats. Activation of the permeability transition pore with PTP activators lonidamine (10 mg/kg body weight) or atractyloside (5 mg/kg body weight) before the sustained ischemia on day 2 resulted in complete abolition of SWOP-mediated cytoprotective effects. These agents had no effect on the cytoprotective effects that took place during the first window of preconditioning.


CONCLUSIONS
The cytoprotective effects of SWOP are dependent on PTP activation state and may involve upregulation of Bcl-2 expression.
Rajesh
Katare Gopalrao
KG
Department of Surgery II, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi, Japan.
Sasaguri
Shiro
S
Zhitian
Zou
Z
Suzuki
Ryoko
R
Asakai
Rei
R
Maeda
Hironori
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D002463:Cell Membrane Permeability; D045304:Cytochromes c / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D000255:Adenosine Triphosphate; D045304:Cytochromes c