Inhibition of Ca2+-calpain signaling is a new mechanism using Laminaria japonica polysaccharide to prevent macrophage foam cell formation and atherosclerosis

Authors：Li, Xue-Ying; Kuang, Dan-Dan; Guo, An-Jun; Deng, Yuan-Yuan; Pan, Li-Hua; Li, Qiang-Ming; Luo, Jian-Ping^*; Zha, Xue-Qiang^*

Source：Food & Function, 2023, 14(9): 4036-4048.

DOI：10.1039/d2fo04099a

• REGULATES AUTOPHAGY
• DEFICIENT
• DISEASE
• MICE
• FLUX
• FAT

The Ca2+-calpain signaling plays a pivotal role in regulating the upstream signaling pathway of cellular autophagy. The aim of the current work was to investigate the role of Ca2+-calpain signaling in the regulation of macrophage autophagy by a Laminaria japonica polysaccharide (LJP61A) in Ox-LDL induced macrophages and high fat diet fed atherosclerotic mice. Results revealed that the LJP61A markedly decreased the levels of intracellular Ca2+, calpain1, calpain2 and their downstream effectors (Gsa, cAMP and IP3), and simultaneously enhanced autophagy activity and lipid metabolism, thereby reducing lipid accumulation in the Ox-LDL stimulated macrophages and lipid-laden plaques in atherosclerotic mice. Moreover, BAPTA-AM (a Ca2+ chelator) and calpeptin (a calpain inhibitor) synergistically strengthened the beneficial effects of LJP61A on autophagy and lipid metabolism by decreasing the levels of intracellular Ca2+, calpain1, calpain2, and their downstream effectors (Gsa, cAMP and IP3) induced by Ox-LDL. These findings suggested that the LJP61A suppressed macrophage derived foam cell formation and atherosclerosis by modulating the Ca2+-calpain-mediated autophagy.

• Institution
  广东省农业科学院