The Role of Class III PI3K/Beclin-1 Autophagy Pathway in Up-Regulation of ETA Receptor in Mesenteric Artery of Mice by mmLDL / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effect of minimally modified low-density lipoprotein (mmLDL) on ETA receptor of mesenteric artery (endothelin type A receptors, ETA) in mice for the first time and whether autophagy is involved in this process. METHODS: Mice were injected mmLDL in the tail vein and intraperitoneally with Class III PI3K autophagy pathway inhibitor 6-amino-3-methylpurine (3-MA) to explore the role of autophagy in mmLDL treated mice. The changes of vasoconstriction curve of mesenteric artery induced by ET-1 (endothelin 1) in mice were observed by a sensitive myograph system. ETA receptor was detected by RT-PCR quantitative mRNA and Western blot. The protein levels of Class III PI3K, Beclin-1, LC3-Ⅱ/, p62 and p-NF-κB, NF-κB were detected by Western blot. RESULTS: The contractility curve of ET-1 induced by mmLDL was significantly enhanced, showing that the Emax value increased from the nomal saline (NS) group (184.87±7.46)% to (319.91±20.31)% (P < 0.001), the pEC50 increased from NS group (8.05±0.05) to (9.11±0.09) (P<0.01). mmLDL up-regulated Class III PI3K,beclin-1,LC3-Ⅱ/ and down-regulated p62 protein level, at the same time, it also caused the ETA receptor mRNA level, protein expression increased significantly, up-regulated the protein level of p-NF-κB; intraperitoneal injection of 3-MA inhibits these effects of mmLDL. CONCLUSION: mmLDL can activate autophagy and down-stream NF-κB pathway through Class III PI3K/Beclin-1 pathway to up-regulate ETA receptor.