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Responses of fas/cytokine‐mediated apoptotic pathway to 12 week treadmill exercise in the aging rat heart
Author(s) -
Kwak HyoBum,
Song Wook,
Kim JongHee,
Lawler John M.
Publication year - 2006
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.20.4.a394-c
Subject(s) - fadd , apoptosis , endocrinology , cytokine , medicine , death domain , ventricle , caspase , fas ligand , caspase 3 , tumor necrosis factor alpha , chemistry , programmed cell death , biochemistry
30% of heart cells may be lost with advancing age through increased cell death due to apoptosis and necrosis. Previously, we demonstrated that exercise training (ET) attenuated age‐induced increases in mitochondria‐mediated apoptosis. Aging increases inflammatory cytokine levels in many tissues including heart. We hypothesized that ET would ameliorate age‐induced changes in fas/cytokine‐mediated apoptotic signaling in the left ventricle. 3 and 24 mo. old Fischer‐344 rats were assigned to young sedentary (YS), young exercise (YE), old sedentary (OS), and old exercise (OE) groups. ET groups ran on a treadmill for 60 min/day, 5 d/wk for additional 12 wks. Fas, p‐FADD (phosphorylated fas‐associating death domain), pro‐caspase‐8, cleaved caspase‐8, and ARC (apoptosis repressor with caspases recruitment domain) protein expression in the left ventricle were measured by Western blot. Pro‐caspase‐8 (+117%) and cleaved caspase‐8 (+140%) levels were markedly elevated with aging, whereas cleaved caspase‐8 was reduced by ET (‐54%) in old rats. p‐FADD levels increased with aging, but there were no training effects on p‐FADD in old groups. Fas was not affected by aging or ET. ARC was not affected by age or ET, but a small trend (+10%) existed in OE compared with YS. Our results indicate that 12 weeks of treadmill exercise training attenuates caspase‐8 cleavage, but are not consistent with a significant contribution by upstream fas/cytokine regulators tested. Supported by Texas Affiliate of the American Heart Association (GIA # 0555064Y)