Possible molecular mechanisms underlying age-related cardiomyocyte apoptosis in the F344XBN rat heart.
Despite advances in treatment, age-related cardiac dysfunction still remains a leading cause of cardiovascular death. Recent data have suggested that increases in cardiomyocyte apoptosis may be involved in the pathological remodeling of heart. Here, we examine the effects of aging on cardiomyocyte apoptosis in 6-, 30-, and 36-month-old Fischer344 x Brown Norway F1 hybrid rats (F344XBN). Compared with 6-month hearts, aged hearts exhibited increased TdT-mediated dUTP nick end labeling-positive nuclei, caspase-3 activation, caspase-dependent cleavage of alpha-fodrin and diminished phosphorylation of protein kinase B/Akt (Thr 308). These age-dependent increases in cardiomyocyte apoptosis were associated with alterations in the composition of the cardiac dystrophin glycoprotein complex and elevated cytoplasmic IgG and albumin immunoreactivity. Immunohistochemical analysis confirmed these data and demonstrated qualitative differences in localization of dystrophin-glycoprotein complex (DGC) molecules with aging. Taken together, these data suggest that aging-related increases in cardiac apoptotic activity model may be due, at least in part, to age-associated changes in DGC structure.
Kakarla
Sunil K
SK
Laboratory of Molecular Physiology, Robert C. Byrd Biotechnology Science Center, Department of Biological Sciences, 1700 3rd Avenue, Marshall University, Huntington, WV 25755-1090, USA.
Rice
Kevin M
KM
Katta
Anjaiah
A
Paturi
Satyanarayana
S
Wu
Miaozong
M
Kolli
Madhukar
M
Keshavarzian
Saba
S
Manzoor
Kamran
K
Wehner
Paulette S
PS
Blough
Eric R
ER
D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049030:Dystroglycans / Q000032:analysis; D049028:Dystrophin-Associated Protein Complex / Q000032:analysis; D020287:In Situ Nick-End Labeling; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D049028:Dystrophin-Associated Protein Complex; D049030:Dystroglycans; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9