NDRG2 is highly expressed in pancreatic beta cells and involved in protection against lipotoxicity.
The N-myc downstream-regulated gene 2 (NDRG2) is involved in cell differentiation and apoptosis, but its function in the pancreas remains to be established. Herein we examine the expression and function of NDRG2 in the endocrine pancreas. NDRG2 immunoreactivity was localized mainly in the cytoplasm of pancreatic beta cells. When beta-TC3 cells were exposed chronically to high levels of free fatty acid (FFA), cell viability was impaired, and Akt and NDRG2 phosphorylation were reduced. NDRG2 is a potential substrate of protein kinase Akt. Overexpression of constitutively active Akt enhanced NDRG2 phosphorylation and abolished the apoptosis induced by FFA in beta-TC3 cells, whereas NDRG2 knock-down attenuated Akt-mediated protection of beta cells against fatty acid-triggered apoptosis. Collectively, these data indicate that NDRG2 acts as a key molecule in pancreatic beta cells and is involved in the Akt-mediated protection of beta cells against lipotoxicity.
Shen
Lan
L
Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, China. lanshen@fmmu.edu.cn
Liu
Xuewu
X
Hou
Wugang
W
Yang
Guodong
G
Wu
Yousheng
Y
Zhang
Rui
R
Li
Xia
X
Che
Honglei
H
Lu
Zifan
Z
Zhang
Yuanqiang
Y
Liu
Xinping
X
Yao
Libo
L
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D005230:Fatty Acids, Nonesterified; C466228:NDRG2 protein, human; C485172:Ndr2 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins