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Melatonin attenuates vascular calcification by inhibiting mitochondria fission via an AMPK/Drp1 signalling pathway
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Melatonin attenuates vascular calcification by inhibiting mitochondria fission via an AMPK/Drp1 signalling pathway
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Journal Article
Melatonin attenuates vascular calcification by inhibiting mitochondria fission via an AMPK/Drp1 signalling pathway
2020
Overview
Mitochondrial fission plays a role in cardiovascular calcification. Melatonin has previously been shown to protect against cardiovascular disease, so this study sought to explore whether it attenuates vascular calcification by regulating mitochondrial fission via the AMP‐activated protein kinase/dynamin‐related protein 1 (AMPK/Drp1) signalling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin red staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure the expression of runt‐related transcription factor 2 (Runx2), Drp1 and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were down‐regulated, Drp1 was reduced in response to melatonin, and this was accompanied by decreased apoptosis. Melatonin also reduced levels of mitochondrial superoxide, reversed β‐glycerophosphate (β‐GP)‐induced ΔΨm dissipation and decreased mitochondrial fragmentation. The effects of melatonin in β‐GP‐treated VSMCs were similar to those of mitochondrial division inhibitor 1. Melatonin significantly activated the expression of AMPK and decreased Drp1 expression. Treatment with compound C ablated the observed benefits of melatonin treatment. These findings indicate that melatonin protects VSMCs against calcification by inhibiting mitochondrial fission via the AMPK/Drp1 pathway.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ AMP
/ AMP-Activated Protein Kinases - antagonists & inhibitors
/ AMP-Activated Protein Kinases - metabolism
/ AMP‐activated protein kinase
/ Animals
/ Calcium
/ Cytoprotection - drug effects
/ Dynamin
/ Kinases
/ Membrane Potential, Mitochondrial - drug effects
/ Mitochondrial Dynamics - drug effects
/ Muscle, Smooth, Vascular - pathology
/ Myocytes, Smooth Muscle - metabolism
/ Original
/ Proteins
/ Signal Transduction - drug effects
/ Vascular Calcification - metabolism
