Sreedhar Remya, Giridharan Vijayasree V, Arumugam Somasundaram, Karuppagounder Vengadeshprabhu, Palaniyandi Suresh S, Krishnamurthy Prasanna, Quevedo Joao, Watanabe Kenichi, Konishi Tetsuya, Thandavarayan Rajarajan A
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX.
Biofactors. 2016 Jul 8;42(4):368-75. doi: 10.1002/biof.1280. Epub 2016 Apr 18.
Heart failure is typically related to aging as there is a definite relationship between age-related changes in the heart and the pathogenesis of heart failure. We have previously reported the involvement of p38 mitogen-activated protein kinase protein in cardiac function using animal models of heart failure. To further understand its relationship with aging-induced heart failure, we have compared its expression in the hearts of senescence accelerated-prone (SAMP8) mice and their control (SAMR1) with normal aging behavior. We have identified its activation along with reduced expression of 14-3-3η protein in SAMP8 mice hearts than in SAMR1 mice. To reveal the downstream signaling, we have measured the endoplasmic reticulum stress marker proteins along with some inflammatory and apoptosis markers and identified a significant increase in SAMP8 mice hearts than that of SAMR1. In addition, we have performed comet assay and revealed a significant DNA damage in the cardiomyocytes of SAMP8 mice when compared with SAMR1 mice. All these results demonstrate the role of 14-3-3η protein and the downstream mitogen-activated protein kinase-mediated endoplasmic reticulum stress, and apoptosis and DNA damage in aging-induced cardiac malfunction in SAMP8 mice. Thus targeting this signaling might be effective in treating age-related cardiac dysfunction. © 2016 BioFactors, 42(4):368-375, 2016.
心力衰竭通常与衰老相关，因为心脏中与年龄相关的变化和心力衰竭的发病机制之间存在明确的关系。我们之前曾利用心力衰竭动物模型报道过p38丝裂原活化蛋白激酶蛋白参与心脏功能。为了进一步了解其与衰老诱导的心力衰竭的关系，我们比较了易衰老（SAMP8）小鼠及其具有正常衰老行为的对照（SAMR1）小鼠心脏中的表达情况。我们发现，与SAMR1小鼠相比，SAMP8小鼠心脏中该蛋白被激活，同时14-3-3η蛋白的表达降低。为了揭示下游信号传导，我们检测了内质网应激标记蛋白以及一些炎症和凋亡标记物，发现SAMP8小鼠心脏中的这些标记物比SAMR1小鼠显著增加。此外，我们进行了彗星试验，结果显示与SAMR1小鼠相比，SAMP8小鼠的心肌细胞存在明显的DNA损伤。所有这些结果都证明了14-3-3η蛋白以及下游丝裂原活化蛋白激酶介导的内质网应激、凋亡和DNA损伤在SAMP8小鼠衰老诱导的心脏功能障碍中的作用。因此，针对这一信号传导途径可能对治疗与年龄相关的心脏功能障碍有效。© 2016生物因子，42(4):368 - 375，2016。
