PMID- 23512717
OWN - NLM
STAT- MEDLINE
DCOM- 20140403
LR  - 20240209
IS  - 1466-1268 (Electronic)
IS  - 1355-8145 (Print)
IS  - 1355-8145 (Linking)
VI  - 18
IP  - 5
DP  - 2013 Sep
TI  - Inhibition of cystathionine beta-synthase is associated with glucocorticoids 
      over-secretion in psychological stress-induced hyperhomocystinemia rat liver.
PG  - 631-41
LID - 10.1007/s12192-013-0416-0 [doi]
AB  - Hyperhomocysteinemia (HHcy), a pathological condition characterized by an 
      increase in plasma concentration of total homocysteine (Hcy), is recognized as a 
      risk factor for several diseases. The transsulfuration pathway is the main 
      metabolic fate of Hcy utilization, which requires the activity of cystathionine 
      beta-synthase (CBS). Our results showed the development of HHcy induced by 
      psychological stress was mainly derived from a reduction of CBS activity in the 
      liver, which was accompanied by a significant decrease in its mRNA level. It 
      suggested that the hepatic CBS enzyme regulated by stress at the level of 
      transcription would have a profound effect on circulating Hcy levels. The 
      expression of Sp3, a negative factor for cbs transcription, obviously increased 
      in hepatocytes nuclei of stressed rats, but Sp1 was not altered. It indicated 
      that Sp3 was the key point of variations in cbs transcription caused by stress. 
      Meanwhile, we detected that augmented plasma Hcy concentrations correlated with 
      glucocordicoids (GCs) over-secretion in response to stress, and CBS mRNA levels 
      were markedly lowered in GCs-treated rat hepatocytes. Further results found that 
      glucocorticoids receptor (GR) expression in hepatocyte nuclei of stress rats and 
      GR nuclear translocation ratio was increased, and the same results were proved by 
      experiments in vitro, i.e., GR nuclear translocation and Sp3 expression was 
      remarkably increased in GCs-treated hepatocytes. Moreover, results from ChIP 
      suggested GCs enhanced the binding of GR to the regulatory region of the Sp3 
      promoter. These results indicated that GCs inhibit CBS transcription by 
      up-regulating Sp3 in psychological stress-induced HHcy.
FAU - Zhao, Yun
AU  - Zhao Y
AD  - Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, 
      China.
FAU - Wu, Shuqing
AU  - Wu S
FAU - Gao, Xiujie
AU  - Gao X
FAU - Zhang, Zhiqing
AU  - Zhang Z
FAU - Gong, Jingbo
AU  - Gong J
FAU - Zhan, Rui
AU  - Zhan R
FAU - Wang, Xinxing
AU  - Wang X
FAU - Wang, Weiming
AU  - Wang W
FAU - Qian, Lingjia
AU  - Qian L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130320
PL  - Netherlands
TA  - Cell Stress Chaperones
JT  - Cell stress & chaperones
JID - 9610925
RN  - 0 (Glucocorticoids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 148710-94-5 (Sp3 Transcription Factor)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - W980KJ009P (Corticosterone)
RN  - Homocysteinemia
SB  - IM
MH  - Animals
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Corticosterone/blood/*pharmacology
MH  - Cystathionine beta-Synthase/antagonists & inhibitors/genetics/*metabolism
MH  - Glucocorticoids/blood/*pharmacology
MH  - Hepatocytes/drug effects/enzymology/metabolism
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/metabolism/pathology
MH  - Male
MH  - Models, Animal
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Glucocorticoid/metabolism
MH  - Sp1 Transcription Factor/genetics/metabolism
MH  - Sp3 Transcription Factor/genetics/metabolism
MH  - *Stress, Psychological
MH  - Up-Regulation/drug effects
PMC - PMC3745252
EDAT- 2013/03/21 06:00
MHDA- 2014/04/04 06:00
PMCR- 2014/03/01
CRDT- 2013/03/21 06:00
PHST- 2012/11/06 00:00 [received]
PHST- 2013/03/01 00:00 [accepted]
PHST- 2013/02/26 00:00 [revised]
PHST- 2013/03/21 06:00 [entrez]
PHST- 2013/03/21 06:00 [pubmed]
PHST- 2014/04/04 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - S1355-8145(23)02068-0 [pii]
AID - 416 [pii]
AID - 10.1007/s12192-013-0416-0 [doi]
PST - ppublish
SO  - Cell Stress Chaperones. 2013 Sep;18(5):631-41. doi: 10.1007/s12192-013-0416-0. 
      Epub 2013 Mar 20.