PMID- 24050301 OWN - NLM STAT- MEDLINE DCOM- 20140401 LR - 20171116 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 61 IP - 41 DP - 2013 Oct 16 TI - Mulberry 1-deoxynojirimycin pleiotropically inhibits glucose-stimulated vascular smooth muscle cell migration by activation of AMPK/RhoB and down-regulation of FAK. PG - 9867-75 LID - 10.1021/jf403636z [doi] AB - Mulberry 1-deoxynojirimycin (DNJ), an inhibitor of alpha-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-kappaB (NF-kappaB) 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. FAU - Chan, Kuei-Chuan AU - Chan KC AD - Department of Internal Medicine, Chung-Shan Medical University Hospital , No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan. FAU - Lin, Ming-Cheng AU - Lin MC FAU - Huang, Chien-Ning AU - Huang CN FAU - Chang, Wen-Chun AU - Chang WC FAU - Wang, Chau-Jong AU - Wang CJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131002 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - 0 (Plant Extracts) RN - 19130-96-2 (1-Deoxynojirimycin) RN - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.6.5.2 (rhoB GTP-Binding Protein) RN - IY9XDZ35W2 (Glucose) SB - IM MH - 1-Deoxynojirimycin/*pharmacology MH - AMP-Activated Protein Kinases/*genetics/metabolism MH - Animals MH - Atherosclerosis/drug therapy/enzymology/genetics/*physiopathology MH - Cell Line MH - Cell Movement/drug effects MH - Down-Regulation/drug effects MH - Enzyme Activation/drug effects MH - Focal Adhesion Protein-Tyrosine Kinases/*genetics/metabolism MH - Glucose/*metabolism MH - Humans MH - Morus/*chemistry MH - Muscle, Smooth, Vascular/cytology/*drug effects/enzymology/metabolism MH - Plant Extracts/*pharmacology MH - Rats MH - Signal Transduction/drug effects MH - rhoB GTP-Binding Protein/genetics/metabolism EDAT- 2013/09/21 06:00 MHDA- 2014/04/02 06:00 CRDT- 2013/09/21 06:00 PHST- 2013/09/21 06:00 [entrez] PHST- 2013/09/21 06:00 [pubmed] PHST- 2014/04/02 06:00 [medline] AID - 10.1021/jf403636z [doi] PST - ppublish SO - J Agric Food Chem. 2013 Oct 16;61(41):9867-75. doi: 10.1021/jf403636z. Epub 2013 Oct 2.