Choi Dong Ho, Lee Su Mi, Park Bin Na, Lee Mi Hwa, Yang Dong Eun, Son Young Ki, Kim Seong Eun, An Won Suk
Department of Internal Medicine, Good Moon Hwa Hospital, Busan 48735, Republic of Korea.
Department of Internal Medicine, Dong-A University, Busan 49201, Republic of Korea.
Biomedicines. 2024 Sep 15;12(9):2107. doi: 10.3390/biomedicines12092107.
Mitochondrial homeostasis is controlled by biogenesis, dynamics, and mitophagy. Mitochondrial dysfunction plays a central role in cardiovascular and renal disease and omega-3 fatty acids (FAs) are beneficial for cardiovascular disease. We investigated whether omega-3 fatty acids (FAs) regulate mitochondrial biogenesis, dynamics, and mitophagy in the kidney and heart of adenine-induced uremic rats. Eighteen male Sprague Dawley rats were divided into normal control, adenine control, and adenine with omega-3 FA groups. Using Western blot analysis, the kidney and heart expression of mitochondrial homeostasis-related molecules, including peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), dynamin-related protein 1 (Drp1), and phosphatase and tensin homolog-induced putative kinase 1 (PINK1) were investigated. Compared to normal, serum creatinine and heart weight/body weight in adenine control were increased and slightly improved in the omega-3 FA group. Compared to the normal controls, the expression of PGC-1α and PINK1 in the kidney and heart of the adenine group was downregulated, which was reversed after omega-3 FA supplementation. Drp1 was upregulated in the kidney but downregulated in the heart in the adenine group. Drp1 expression in the heart recovered in the omega-3 FA group. Mitochondrial DNA (mtDNA) was decreased in the kidney and heart of the adenine control group but the mtDNA of the heart was recovered in the omega-3 FA group. Drp1, which is related to mitochondrial fission, may function oppositely in the uremic kidney and heart. Omega-3 FAs may be beneficial for mitochondrial homeostasis by activating mitochondrial biogenesis and PINK1-dependent mitophagy in the kidney and heart of uremic rats.
线粒体稳态由生物发生、动力学和线粒体自噬控制。线粒体功能障碍在心血管和肾脏疾病中起核心作用，而ω-3脂肪酸（FAs）对心血管疾病有益。我们研究了ω-3脂肪酸是否调节腺嘌呤诱导的尿毒症大鼠肾脏和心脏中的线粒体生物发生、动力学和线粒体自噬。18只雄性Sprague Dawley大鼠分为正常对照组、腺嘌呤对照组和腺嘌呤加ω-3脂肪酸组。采用蛋白质免疫印迹分析，研究了肾脏和心脏中线粒体稳态相关分子的表达，包括过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）、动力相关蛋白1（Drp1）和磷酸酶和张力蛋白同源物诱导的假定激酶1（PINK1）。与正常组相比，腺嘌呤对照组的血清肌酐和心脏重量/体重增加，而ω-3脂肪酸组略有改善。与正常对照组相比，腺嘌呤组肾脏和心脏中PGC-1α和PINK1的表达下调，补充ω-3脂肪酸后逆转。腺嘌呤组中，Drp1在肾脏中上调，但在心脏中下调。ω-3脂肪酸组心脏中Drp1的表达恢复。腺嘌呤对照组肾脏和心脏中的线粒体DNA（mtDNA）减少，但ω-3脂肪酸组心脏中的mtDNA恢复。与线粒体分裂相关的Drp1在尿毒症肾脏和心脏中的作用可能相反。ω-3脂肪酸可能通过激活尿毒症大鼠肾脏和心脏中的线粒体生物发生和PINK1依赖性线粒体自噬，对线粒体稳态有益。
