Mulberry 1-deoxynojirimycin pleiotropically inhibits glucose-stimulated vascular smooth muscle cell migration by activation of AMPK/RhoB and down-regulation of FAK.
Mulberry 1-deoxynojirimycin (DNJ), an inhibitor of α-glucosidase, has been reported to help prevent diabetes mellitus and suppress lipid accumulation. The aim of this study was to determine whether mulberry DNJ has pleiotropic effects on the development of atherosclerosis. The mechanisms by which mulberry DNJ might inhibit migration of A7r5 vascular smooth muscle cells (VSMCs) under hyperglycemic conditions mimicking diabetes were investigated. The antimigratory effects of DNJ on VSMCs were assessed by Western blot analysis of migration-related proteins and by electric cell-substrate impedance sensing (ECIS) and visualization of F-actin cytoskeleton. Two pathways of DNJ-mediated inhibition of VSMC migration were identified. The first involved AMPK activation to inhibit fatty acid synthase (FASN) and Akt activity and then RhoB activation to inhibit nuclear factor-κB (NF-κB) and matrix metalloproteinase-2 (MMP) activity. The second involved inhibition of focal adhesion kinase (FAK), Ras, and RhoA activity leading to inhibition of F-actin activity.
Department of Internal Medicine, Chung-Shan Medical University Hospital , No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan.
Kuei-Chuan
KC
Chan
Ming-Cheng
MC
Lin
Chien-Ning
CN
Huang
Wen-Chun
WC
Chang
Chau-Jong
CJ
Wang
D017485:1-Deoxynojirimycin / Q000494:pharmacology*; D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D031625:Morus / Q000737:chemistry*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D010936:Plant Extracts; D017485:1-Deoxynojirimycin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D055372:AMP-Activated Protein Kinases; D020743:rhoB GTP-Binding Protein; D005947:Glucose