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Influence of aging on the interaction of the PI3K survival pathway and the p53‐mediated apoptosis pathway in a rat model of myocardial ischemia‐reperfusion
Author(s) -
Liu Peitan,
Xu Baohuan,
Cavalieri Thomas A.,
Hock Carl E.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.750.8
Subject(s) - apoptosis , ischemia , pi3k/akt/mtor pathway , programmed cell death , medicine , dna fragmentation , ly294002 , fragmentation (computing) , necrosis , cardiac function curve , endocrinology , andrology , chemistry , pharmacology , biology , heart failure , biochemistry , ecology
Cardiomyocyte death induced by myocardial ischemia‐reperfusion (MI/R) can occur via apoptosis and/or necrosis, depending on the ischemic intensity and available survival signals. Aging may alter the balance between survival and apoptotic signals, thereby influencing cell fate. A rat model of MI/R has been used to investigate the cross‐talk between the PI3K survival pathway and the p53‐dependent apoptosis pathway. Our results indicate that inhibition of p53 transcriptional function by pifithrin‐α improved cardiac index (79±11 vs 38±9 ml/min/100g BW, p<0.05) and reduced myocyte apoptosis (96±11 vs 158±17 cells/20 HPF, p<0.05). Moreover, inhibition of PI3K by LY294002 worsened cardiac index (46.3±7 vs 68.3±9 ml/min/100g BW, p<0.05) and increased DNA fragmentation (344±57 vs 118±21 Vmax %, p<0.05), when compared to rats treated with vehicle. Interestingly, treatment of aged MI/R rats with LY increased the expression of p53, compared to young MI/R rats given LY. These results suggest that an interaction exists between the PI3K survival pathway and the p53‐mediated apoptosis pathway during MI/R, and that this interaction may be influenced by aging.