PMID- 23670941
OWN - NLM
STAT- MEDLINE
DCOM- 20140324
LR  - 20220317
IS  - 1930-739X (Electronic)
IS  - 1930-7381 (Linking)
VI  - 21
IP  - 8
DP  - 2013 Aug
TI  - Endogenous oxidative stress, but not ER stress, induces hypoxia-independent 
      VEGF120 release through PI3K-dependent pathways in 3T3-L1 adipocytes.
PG  - 1625-34
LID - 10.1002/oby.20206 [doi]
AB  - OBJECTIVE: Expressions of vascular endothelial growth factor (VEGF) are increased 
      in obese adipocytes and is secreted from obese adipose tissue through 
      hypoxia-independent pathways. Therefore, we investigated the hypoxia-independent 
      mechanism underlying increased expression and release of VEGF in obese 
      adipocytes. DESIGN AND METHODS: We compared signal transduction pathways 
      regulating VEGF with those regulating monocyte chemoattractant protein-1 (MCP-1), 
      which is increased in obese adipocytes, in an in vitro model of artificially 
      hypertrophied 3T3-L1 adipocytes preloaded with palmitate, without the influence 
      of hypoxia. RESULTS: Palmitate-preloaded cells exhibited significantly enhanced 
      oxidative stress (P < 0.01) and showed increased VEGF120 and MCP-1 release (P < 
      0.01, respectively), while endoplasmic reticulum (ER) stress was not induced. 
      Increased VEGF120 release was significantly decreased with PI3K inhibitor 
      LY294002 (P < 0.01). In addition, antioxidant N-acetyl-cysteine (NAC) markedly 
      diminished not only VEGF120 secretion (P < 0.01) but also augmented Akt 
      phosphorylation on Ser473 (P < 0.01). In contrast, increased MCP-1 release was 
      suppressed with JNK inhibitor SP600125 and p38 MAPK inhibitor SB203580 (P < 
      0.01). CONCLUSIONS: VEGF120 release from hypertrophied adipocytes can be enhanced 
      through PI3K pathways activated by oxidative stress but not by ER stress, 
      suggesting that VEGF120 secretion is regulated through oxidative stress-dependent 
      pathways distinct from those involved in MCP-1 release through either JNK or p38 
      MAPK activation.
CI  - Copyright (c) 2012 The Obesity Society.
FAU - Takahashi, Kazuto
AU  - Takahashi K
AD  - Third Department of Internal Medicine, Kyorin University School of Medicine, 
      Mitaka, Tokyo, Japan.
FAU - Miyokawa-Gorin, Kaoru
AU  - Miyokawa-Gorin K
FAU - Handa, Keiko
AU  - Handa K
FAU - Kitahara, Atsuko
AU  - Kitahara A
FAU - Moriya, Rie
AU  - Moriya R
FAU - Onuma, Hirohisa
AU  - Onuma H
FAU - Sumitani, Yoshikazu
AU  - Sumitani Y
FAU - Tanaka, Toshiaki
AU  - Tanaka T
FAU - Katsuta, Hidenori
AU  - Katsuta H
FAU - Nishida, Susumu
AU  - Nishida S
FAU - Yoshimoto, Katsuhiko
AU  - Yoshimoto K
FAU - Ohno, Hideki
AU  - Ohno H
FAU - Ishida, Hitoshi
AU  - Ishida H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130513
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromones)
RN  - 0 (Imidazoles)
RN  - 0 (Morpholines)
RN  - 0 (Palmitates)
RN  - 0 (Pyridines)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Acetylcysteine/pharmacology
MH  - Adipocytes/cytology/metabolism
MH  - Animals
MH  - Cell Hypoxia
MH  - Chemokine CCL2/metabolism
MH  - Chromones/pharmacology
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Imidazoles/pharmacology
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Oxidative Stress/*physiology
MH  - Palmitates/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyridines/pharmacology
MH  - Signal Transduction
MH  - Vascular Endothelial Growth Factor A/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2013/05/15 06:00
MHDA- 2014/03/25 06:00
CRDT- 2013/05/15 06:00
PHST- 2011/09/28 00:00 [received]
PHST- 2012/11/14 00:00 [accepted]
PHST- 2013/05/15 06:00 [entrez]
PHST- 2013/05/15 06:00 [pubmed]
PHST- 2014/03/25 06:00 [medline]
AID - 10.1002/oby.20206 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2013 Aug;21(8):1625-34. doi: 10.1002/oby.20206. Epub 
      2013 May 13.