PMID- 28087344
OWN - NLM
STAT- MEDLINE
DCOM- 20171006
LR  - 20220317
IS  - 0167-4889 (Print)
IS  - 0167-4889 (Linking)
VI  - 1864
IP  - 4
DP  - 2017 Apr
TI  - Up-regulation of the active form of small GTPase Rab13 promotes macroautophagy in 
      vascular endothelial cells.
PG  - 613-624
LID - S0167-4889(17)30005-8 [pii]
LID - 10.1016/j.bbamcr.2017.01.003 [doi]
AB  - The importance of macroautophagy (hereafter referred to as autophagy) in vascular 
      endothelial cell (VEC) biology and dysfunction is increasingly recognized, but 
      the molecular mechanisms of autophagy in VECs in the presence of serum are still 
      poorly understood. Previously, we identified pterostilbene as a potent autophagy 
      inducer of VECs in the presence of serum. In this study, we used pterostilbene as 
      a tool to induce VEC autophagy and identified the differentially expressed genes 
      using high-throughput DAN microarray. The small GTPase Ras-related protein in 
      brain 13 (Rab13) was found to be the most significantly up-regulated gene in 
      pterostilbene-treated human umbilical VECs (HUVECs). Knockdown of Rab13 blocked 
      pterostilbene-induced mTOR inhibition and autophagy, whereas overexpression of 
      the GTP-containing active form of Rab13 induced mTOR inhibition and autophagy in 
      HUVECs. Using a combination of immunofluorescence and co-immunoprecipitation 
      (co-IP) assays, we demonstrated that pterostilbene or up-regulation of the active 
      form of Rab13 promoted the interaction between Rab13 and growth factor 
      receptor-bound protein 2 (Grb2). Knockdown of Grb2 suppressed pterostilbene or 
      up-regulation of the active form of Rab13-induced autophagy. Further mechanistic 
      studies revealed that Rab13 activated the downstream AMP-activated protein kinase 
      (AMPK) and blocked mammalian target of rapamycin (mTOR) signaling by its 
      functional interaction with Grb2 to regulate autophagy in HUVECs. Our study 
      firmly establishes Rab13 as a novel regulator of autophagy in VECs under 
      nutrient-enriched conditions.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Zhang, Lu
AU  - Zhang L
AD  - College of Bioengineering, Henan University of Technology, Lianhua Street, 
      Zhengzhou 450001, China. Electronic address: chaperones@163.com.
FAU - Dai, Fang
AU  - Dai F
AD  - State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 
      730000, China.
FAU - Cui, LiuQing
AU  - Cui L
AD  - College of Bioengineering, Henan University of Technology, Lianhua Street, 
      Zhengzhou 450001, China.
FAU - Zhou, Bo
AU  - Zhou B
AD  - State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 
      730000, China.
FAU - Guo, YuQi
AU  - Guo Y
AD  - Henan Provincial People's Hospital, Zhengzhou 450003, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170110
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Res
JT  - Biochimica et biophysica acta. Molecular cell research
JID - 101731731
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (GRB2 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Stilbenes)
RN  - 26R60S6A5I (pterostilbene)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.6.1.- (RAB13 protein, human)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - AMP-Activated Protein Kinases/*genetics/metabolism
MH  - Autophagy/drug effects/*genetics
MH  - GRB2 Adaptor Protein/antagonists & inhibitors/*genetics/metabolism
MH  - Gene Expression Regulation
MH  - Human Umbilical Vein Endothelial Cells/cytology/drug effects/metabolism
MH  - Humans
MH  - Oligonucleotide Array Sequence Analysis
MH  - Protein Binding
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction
MH  - Stilbenes/pharmacology
MH  - TOR Serine-Threonine Kinases/*genetics/metabolism
MH  - rab GTP-Binding Proteins/antagonists & inhibitors/*genetics/metabolism
OTO - NOTNLM
OT  - AMP-activated protein kinase
OT  - Growth factor receptor-bound protein 2
OT  - Macroautophagy
OT  - Pterostilbene
OT  - Small GTPase Rab13
OT  - Vascular endothelial cell
EDAT- 2017/01/15 06:00
MHDA- 2017/10/07 06:00
CRDT- 2017/01/15 06:00
PHST- 2016/10/21 00:00 [received]
PHST- 2016/12/21 00:00 [revised]
PHST- 2017/01/06 00:00 [accepted]
PHST- 2017/01/15 06:00 [pubmed]
PHST- 2017/10/07 06:00 [medline]
PHST- 2017/01/15 06:00 [entrez]
AID - S0167-4889(17)30005-8 [pii]
AID - 10.1016/j.bbamcr.2017.01.003 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Res. 2017 Apr;1864(4):613-624. doi: 
      10.1016/j.bbamcr.2017.01.003. Epub 2017 Jan 10.