Details

Autor(en) / Beteiligte

• Zhu, Yi
• Ji, Jing-Jing
• Yang, Rui
• Han, Xi-Qiong
• Sun, Xue-Jiao
• Ma, Wen-Qi
• Liu, Nai-Feng

Titel

Lactate accelerates calcification in VSMCs through suppression of BNIP3-mediated mitophagy

Ist Teil von

• Cellular signalling, 2019-06, Vol.58, p.53-64

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Arterial media calcification is one of the major complications of diabetes mellitus, which is related to oxidative stress and apoptosis. Mitophagy is a special regulation of mitochondrial homeostasis and takes control of intracellular ROS generation and apoptotic pathways. High circulating levels of lactate usually accompanies diabetes. The potential link between lactate, mitophagy and vascular calcification is investigated in this study. Lactate treatment accelerated VSMC calcification, evaluated by measuring the calcium content, ALP activity, RUNX2, BMP-2 protein levels, and Alizarin red S staining. Lactate exposure caused excessive intracellular ROS generation and VSMC apoptosis. Lactate also impaired mitochondrial function, determined by mPTP opening rate, mitochondrial membrane potential and mitochondrial biogenesis markers. Western blot analysis of LC3-II and p62 and mRFP-GFP-LC3 adenovirus detection for autophagy flux revealed that lactate blocked autophagy flux. LC3-II co-staining with LAMP-1 and autophagosome quantification revealed lactate inhibited autophagy. Furthermore, lactate inhibited mitophagy, which was confirmed by TOMM20 and BNIP3 protein levels, LC3-II colocalization with BNIP3 and TEM assays. In addition, BNIP3-mediated mitophagy played a protective role against VSMC calcification in the presence of lactate. This study suggests that lactate accelerates osteoblastic phenotype transition of VSMC and calcium deposition partly through the BNIP3-mediated mitophagy deficiency induced oxidative stress and apoptosis. •Lactate accelerates VSMC calcification through mitochondrial dysfunction.•Lactate disturbes the balance of mitochondrial injury and clearance.•Mitophagy inhibits VSMC calcification by attenuating mitochondrial disorder.