PMID- 17869220
OWN - NLM
STAT- MEDLINE
DCOM- 20071126
LR  - 20211203
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 363
IP  - 2
DP  - 2007 Nov 16
TI  - Unexpected blockade of adipocyte differentiation by K-7174: implication for 
      endoplasmic reticulum stress.
PG  - 355-60
AB  - Preadipocytes constitutively express GATA-2 and GATA-3 that are required to halt 
      the cells at the undifferentiated stage. However, we unexpectedly found that 
      K-7174, a GATA-specific inhibitor, did not induce but rather inhibited 
      differentiation of 3T3-L1 preadipocytes. It was associated with lack of lipid 
      accumulation, blunted expression of adipocyte markers including adiponectin and 
      peroxisome proliferator-activated receptor gamma (PPARgamma), and sustained 
      expression of a preadipocyte marker monocyte chemoattractant protein 1 (MCP-1). 
      Subsequent experiments revealed that K-7174 had the potential to induce 
      endoplasmic reticulum (ER) stress evidenced by induction of GRP78 and CHOP. Other 
      inducers of ER stress completely reproduced the effects of K-7174 including 
      suppression of lipid accumulation, blockade of induction of adiponection and 
      PPARgamma and maintenance of MCP-1 expression. These results indicated a 
      possibility that ER stress suppresses adipocyte differentiation and that GATA 
      inhibitor K-7174 has the potential for interfering with adipogenesis through 
      induction of ER stress.
FAU - Shimada, Tsuyoshi
AU  - Shimada T
AD  - Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine 
      and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 
      409-3898, Japan.
FAU - Hiramatsu, Nobuhiko
AU  - Hiramatsu N
FAU - Okamura, Maro
AU  - Okamura M
FAU - Hayakawa, Kunihiro
AU  - Hayakawa K
FAU - Kasai, Ayumi
AU  - Kasai A
FAU - Yao, Jian
AU  - Yao J
FAU - Kitamura, Masanori
AU  - Kitamura M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070906
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Anisoles)
RN  - 0 (Azepines)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (GATA Transcription Factors)
RN  - 0 (Hspa5 protein, mouse)
RN  - 36376CA57N (K 7174)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*cytology/drug effects/*physiology
MH  - Animals
MH  - Anisoles/*administration & dosage
MH  - Azepines/*administration & dosage
MH  - Cell Differentiation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Endoplasmic Reticulum/drug effects/*physiology/*ultrastructure
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - GATA Transcription Factors/*metabolism
MH  - Mice
MH  - Oxidative Stress/drug effects/*physiology
EDAT- 2007/09/18 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/09/18 09:00
PHST- 2007/08/27 00:00 [received]
PHST- 2007/08/28 00:00 [accepted]
PHST- 2007/09/18 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/09/18 09:00 [entrez]
AID - S0006-291X(07)01904-3 [pii]
AID - 10.1016/j.bbrc.2007.08.167 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2007 Nov 16;363(2):355-60. doi: 
      10.1016/j.bbrc.2007.08.167. Epub 2007 Sep 6.