Laboratory of Molecular Physiology, Robert C. Byrd Biotechnology Science Center, Department of Biological Sciences, 1700 3rd Avenue, Marshall University, Huntington, WV 25755-1090, USA.
J Gerontol A Biol Sci Med Sci. 2010 Feb;65(2):147-55. doi: 10.1093/gerona/glp203. Epub 2010 Jan 7.
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.
尽管在治疗方面取得了进展，但与年龄相关的心脏功能障碍仍然是心血管死亡的主要原因。最近的数据表明，心肌细胞凋亡的增加可能与心脏的病理性重塑有关。在这里，我们研究了年龄对 6 个月、30 个月和 36 个月大的 Fischer344xBrownNorwayF1 杂交大鼠（F344XBN）心肌细胞凋亡的影响。与 6 个月大的心脏相比，衰老的心脏表现出 TdT 介导的 dUTP 缺口末端标记阳性核增加、半胱天冬酶-3 激活、半胱天冬酶依赖性切割α- fodrin 和蛋白激酶 B/Akt（Thr308）磷酸化减少。这些与年龄相关的心肌细胞凋亡增加与心脏营养不良蛋白糖蛋白复合物组成的改变以及细胞质 IgG 和白蛋白免疫反应性的升高有关。免疫组织化学分析证实了这些数据，并表明随着年龄的增长，营养不良蛋白糖蛋白复合物（DGC）分子的定位存在定性差异。总之，这些数据表明，与年龄相关的心脏凋亡活性增加模型可能至少部分是由于 DGC 结构的年龄相关变化引起的。
