Myocyte apoptosis during acute myocardial infarction in rats is related to early sarcolemmal translocation of annexin A5 in border zone.
Annexin A5 is a Ca2+-dependent phospholipid binding protein well known for its high phosphatidylserine affinity. In vitro, translocation to sarcolemma and externalization of endogenous annexin A5 in the cardiomyocyte has recently been demonstrated to exert a proapoptotic effect. To determine whether these in vitro findings occurred in vivo, we performed myocardial infarction (MI) and studied the time course of apoptosis and annexin A5 localization (0.5 to 8 h) in the border zone around the infarcted area. This zone that was defined as Evans blue unstained and triphenyltetrazolium chloride (TTC) stained, represented 42.3 +/- 5.5% of the area at risk and showed apoptotic characteristics (significant increases in caspase 3 activity 2.3-fold at 0.5 h; P < 0.05), transferase-mediated dUTP nick-end labeling-positive cardiomyocytes (15.8 +/- 0.8% at 8 h), and DNA ladder. When compared with sham-operated rats, we found that in this area, annexin A5 was translocated to the sarcolemma as early as 0.5 h after MI and that translocation increased with time. Moreover, the amount of annexin A5 was unchanged in the border zone and decreased in the infarcted area after 1 h (77.1 +/- 4.8%; P < 0.01 vs. perfused area), suggesting a release in the latter but not in the former. In conclusion, we demonstrated that annexin A5 translocation is an early and rapid event of the whole border zone, likely due to Ca2+ increase. Part of this translocation occurred in areas where apoptosis was later detected and suggests that in vivo as in vitro annexin A5 might be involved in the regulation of early apoptotic events during cardiac pathological situations.
Monceau
Virginie
V
Institut National de la Santé et de la Recherche Médicale (INSERM) U-689, Centre de Recherche Cardiovasculaire INSERM-Lariboisière, Paris Cedex 10, France.
Belikova
Yulia
Y
Kratassiouk
Gueorgui
G
Robidel
Estelle
E
Russo-Marie
Françoise
F
Charlemagne
Daniele
D
D000208:Acute Disease; D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003331:Coronary Vessels / Q000502:physiology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D020287:In Situ Nick-End Labeling; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000473:pathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D017304:Annexin A5; D004247:DNA; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D000254:Sodium-Potassium-Exchanging ATPase