PMID- 21935927
OWN - NLM
STAT- MEDLINE
DCOM- 20111115
LR  - 20220408
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 226
IP  - 11
DP  - 2011 Nov
TI  - TRB3 mediates homocysteine-induced inhibition of endothelial cell proliferation.
PG  - 2782-9
LID - 10.1002/jcp.22554 [doi]
AB  - Hyperhomocysteinemia (HHcy) has been shown to induce endothelial dysfunction, an 
      early event in the progression of atherosclerosis. However, the underlying 
      mechanism of endothelial cell injury in HHcy has not been clearly elucidated. In 
      this study, we examined the effect of homocysteine on tribbles-related protein 3 
      (TRB3)-mediated cell-cycle arrest in human umbilical vein endothelial cells 
      (HUVECs). Treatment of HUVECs with homocysteine (0-250 micromol/L) resulted in 
      inhibition of cell proliferation assessed by [(3)H]-thymidine incorporation into 
      DNA. Homocysteine induced cell-cycle arrest in the G1 phase by up-regulating the 
      protein levels of p27(kip1). Under these conditions, homocysteine did not induce 
      endoplasmic reticulum stress. However, homocysteine up-regulated the expression 
      of TRB3, thus leading to the dephosphorylation of Akt (Thr308). Knock-down of 
      endogenous TRB3 using siRNA significantly suppressed the inhibitory effect of 
      homocysteine on the proliferation of HUVECs. Homocysteine-induced TRB3 expression 
      was mediated by the cAMP/cAMP response element-binding protein (CREB) pathway. 
      These results demonstrate that TRB3 is a critical molecule in the 
      homocysteine-mediated cell-cycle arrest in endothelial cells.
CI  - Copyright (c) 2011 Wiley-Liss, Inc.
FAU - Zou, Tong
AU  - Zou T
AD  - Department of Cardiology, Beijing Hospital, Beijing, China.
FAU - Liu, Wen-Jing
AU  - Liu WJ
FAU - Li, Shu-De
AU  - Li SD
FAU - Zhou, Wei
AU  - Zhou W
FAU - Yang, Jie-Fu
AU  - Yang JF
FAU - Zou, Cheng-Gang
AU  - Zou CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (CDKN1B protein, human)
RN  - 0 (CREB1 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
RN  - 0 (TRIB3 protein, human)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Cell Cycle Proteins/genetics/*metabolism
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p27/metabolism
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Gene Knockdown Techniques
MH  - Homocysteine/*pharmacology
MH  - Humans
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Repressor Proteins/genetics/*metabolism
MH  - Up-Regulation
EDAT- 2011/09/22 06:00
MHDA- 2011/11/16 06:00
CRDT- 2011/09/22 06:00
PHST- 2011/09/22 06:00 [entrez]
PHST- 2011/09/22 06:00 [pubmed]
PHST- 2011/11/16 06:00 [medline]
AID - 10.1002/jcp.22554 [doi]
PST - ppublish
SO  - J Cell Physiol. 2011 Nov;226(11):2782-9. doi: 10.1002/jcp.22554.