Beta-VLDL induced VLDL-R's up-regulation via PKC-ERK1/2 signal pathway.
To explore the intracellular signal pathways for beta-VLDL induced very low density lipoprotein receptor (VLDL-R) transcription up-regulation and their effects on lipid accumulation in macrophages, Western Blot was used to examine phosphorylated ERK1/2 protein and regulated effects by different singal kinase inhibitants. It was found that beta-VLDL induced an increase in ERK1/2 activity in a protein kinase C (PKC)-dependent manner in murine RAW264.7 macrophages. By using different protein kinases inhibitors or activators, it was observed that the effect of beta-VLDL induced VLDL receptor transcription, which was monitored by RT-PCR analysis of VLDL receptor mRNA, was not affected by the inhibitor of p38 kinase and cAMP analog, but extremely abolished by pretreating cells with PD98059, an inhibitor of ERK and GF 109203X, an inhibitor of PKC. These results demonstrated that the PKC-ERK1/2 cascade is the essential signaling pathway by which beta-VLDL activated VLDL-R mRNA expression. Inhibition of the ERK1/2 signaling cascade resulted in suppression of the cellular lipid accumulation induced by beta-VLDL in macrophages.
Liu
Zhiguo
Z
Department of Biotechnology and Chemical Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Wang
Yan
Y
Qu
Shen
S
Feng
Youmei
Y
Wu
Fan
F
Zong
Yiqiang
Y
Zhao
Zechun
Z
D002478:Cells, Cultured; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014157:Transcription Factors; C036053:VLDL receptor; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3