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Diminished substrate‐mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats
IUBMB Life ( IF 4.6 ) Pub Date : 2021-01-22 , DOI: 10.1002/iub.2449
Sasikala Rajendran Raji 1 , Ravikumar Jayakumari Nandini 1 , Sivasailam Ashok 1 , Chellappan Reghuvaran Anand 1 , Velayudhan Pillai Vivek 2 , Karunakaran Jayakumar 2 , Vijayakumar Sreelatha Harikrishnan 3 , Shankarappa Manjunatha 4 , Srinivas Gopala 1
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OBJECTIVE Heart diseases are common in the offspring of gestational diabetic mother (ODM). Defects in mitochondrial metabolism and autophagy may, in part, be responsible for the adverse structural and functional alterations in the heart. The principal objective of this study was to investigate cardiac mitochondrial respiration and autophagy in male and female offspring of diabetic pregnancy at two different developmental stages of life, weaning and adult. METHODS Male and female offspring of rats with streptozotocin-induced gestational diabetes were used for the study and compared with offspring of control (non-diabetic) mother (OCM) rats. High-resolution respirometry was used to measure substrate-mediated respiration in mitochondria isolated from ventricular tissues of ODM and OCM. Expression of proteins associated with autophagy and oxidative stress was examined by western blot analysis. RESULTS Mitochondrial complex I and complex II respiration was significantly reduced in adult male ODM while it was unaltered or less affected in weaning male, adult and weaning female ODM. Elevated autophagy was observed in adult male but not in adult female ODM. Expression of oxidative stress markers was observed to be similar in all the groups. CONCLUSION Altered cardiac mitochondrial respiration and autophagy were observed in adult male ODM compared to OCM, while the male and female offspring at weaning stage were less affected. The results of the study show that maternal hyperglycemia affects mitochondrial respiration and autophagy in the ODM heart, which may potentially be responsible for the cardiovascular complications observed in adult life. This article is protected by copyright. All rights reserved.

中文翻译:

妊娠期糖尿病大鼠成年雄性后代的底物介导的心脏线粒体呼吸减少和自噬升高

目的心脏病在妊娠糖尿病母亲(ODM)的后代中很常见。线粒体代谢和自噬的缺陷可能部分是造成心脏结构和功能不良改变的原因。本研究的主要目的是调查在生命的两个不同发育阶段(断奶和成年)的糖尿病妊娠男性和女性后代的心脏线粒体呼吸和自噬。方法 使用链脲佐菌素诱导的妊娠糖尿病大鼠的雄性和雌性后代进行研究,并与对照(非糖尿病)母亲(OCM)大鼠的后代进行比较。高分辨率呼​​吸测定法用于测量从 ODM 和 OCM 的心室组织中分离的线粒体中底物介导的呼吸。通过蛋白质印迹分析检查与自噬和氧化应激相关的蛋白质的表达。结果线粒体复合物I和复合物II呼吸在成年雄性ODM中显着降低,而在断奶雄性、成年和断奶雌性ODM中未改变或受影响较小。在成年男性中观察到升高的自噬,但在成年女性 ODM 中未观察到。在所有组中观察到氧化应激标志物的表达相似。结论与OCM相比,成年雄性ODM的心脏线粒体呼吸和自噬发生改变,而断奶期的雄性和雌性后代受到的影响较小。研究结果表明,母体高血糖会影响 ODM 心脏中的线粒体呼吸和自噬,这可能是成年生活中观察到的心血管并发症的潜在原因。本文受版权保护。版权所有。
更新日期:2021-01-22
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