Abstract：
BACKGROUND: Myocardial infarction (MI) is a significant cause of death in diabetic patients. Growing evidence suggests that mitochondrial dysfunction contributes to heart failure in diabetes. However, the molecular mechanisms of mitochondrial dysfunction mediating heart failure in diabetes are still poorly understood.
METHODS: We examined MRPL12 levels in right atrial appendage tissues from diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Using AC-16 cells overexpressing MRPL12 under normal and hyperglycemic conditions we performed mitochondrial functional assays OXPHOS, bioenergetics, mitochondrial membrane potential, ATP production and cell death.
RESULTS: We observed elevated MRPL12 levels in heart tissue samples from diabetic patients with ischemic heart disease compared to non-diabetic patients. Overexpression of MRPL12 under hyperglycemic conditions did not affect oxidative phosphorylation (OXPHOS) levels, cellular ATP levels, or cardiomyocyte cell death. However, notable impairment in mitochondrial membrane potential (MMP) was observed under hyperglycemic conditions, along with alterations in both basal respiration oxygen consumption rate (OCR) and maximal respiratory capacity OCR.
CONCLUSIONS: Overall, our results suggest that MRPL12 may have a compensatory role in the diabetic myocardium with ischemic heart disease, suggesting that MRPL12 may implicate in the pathophysiology of MI in diabetes.
METHODS: We examined MRPL12 levels in right atrial appendage tissues from diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Using AC-16 cells overexpressing MRPL12 under normal and hyperglycemic conditions we performed mitochondrial functional assays OXPHOS, bioenergetics, mitochondrial membrane potential, ATP production and cell death.
RESULTS: We observed elevated MRPL12 levels in heart tissue samples from diabetic patients with ischemic heart disease compared to non-diabetic patients. Overexpression of MRPL12 under hyperglycemic conditions did not affect oxidative phosphorylation (OXPHOS) levels, cellular ATP levels, or cardiomyocyte cell death. However, notable impairment in mitochondrial membrane potential (MMP) was observed under hyperglycemic conditions, along with alterations in both basal respiration oxygen consumption rate (OCR) and maximal respiratory capacity OCR.
CONCLUSIONS: Overall, our results suggest that MRPL12 may have a compensatory role in the diabetic myocardium with ischemic heart disease, suggesting that MRPL12 may implicate in the pathophysiology of MI in diabetes.
摘要：
背景：心肌梗死（MI）是糖尿病患者死亡的重要原因。越来越多的证据表明，线粒体功能障碍有助于糖尿病患者的心力衰竭。然而,线粒体功能障碍介导糖尿病心力衰竭的分子机制仍然知之甚少。
方法：本研究旨在探讨线粒体核糖体蛋白L7/L12（MRPL12）在人类心脏中的作用。线粒体耗氧率和膜电位分别使用海马分析和共聚焦显微镜测定。数据通过使用组的平均值进行分析，使用学生t检验（对于2组）和ANOVA进行比较，随后进行Tukey测试（对于>2组）。
结果：我们发现，与非糖尿病患者相比，患有缺血性心脏病的糖尿病患者的心脏组织样本中MRPL12水平升高。随着高血糖条件下MRPL12的过度表达，氧化磷酸化水平（OXPHOS）被下调，但是细胞ATP和人心肌细胞死亡保持不变，然而,在高血糖情况下，线粒体膜电位（MMP）明显受损，随着基础呼吸耗氧率（OCR）和最大呼吸容量OCR的变化。
结论：总体而言，我们的结果表明，MRPL12可能在缺血性心脏病的糖尿病心肌中具有代偿作用，提示MRPL12可能与糖尿病MI的病理生理有关。
方法：本研究旨在探讨线粒体核糖体蛋白L7/L12（MRPL12）在人类心脏中的作用。线粒体耗氧率和膜电位分别使用海马分析和共聚焦显微镜测定。数据通过使用组的平均值进行分析，使用学生t检验（对于2组）和ANOVA进行比较，随后进行Tukey测试（对于>2组）。
结果：我们发现，与非糖尿病患者相比，患有缺血性心脏病的糖尿病患者的心脏组织样本中MRPL12水平升高。随着高血糖条件下MRPL12的过度表达，氧化磷酸化水平（OXPHOS）被下调，但是细胞ATP和人心肌细胞死亡保持不变，然而,在高血糖情况下，线粒体膜电位（MMP）明显受损，随着基础呼吸耗氧率（OCR）和最大呼吸容量OCR的变化。
结论：总体而言，我们的结果表明，MRPL12可能在缺血性心脏病的糖尿病心肌中具有代偿作用，提示MRPL12可能与糖尿病MI的病理生理有关。
