PMID- 25520741
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141218
LR  - 20200930
IS  - 1743-7075 (Print)
IS  - 1743-7075 (Electronic)
IS  - 1743-7075 (Linking)
VI  - 11
IP  - 1
DP  - 2014
TI  - Homocysteine downregulates gene expression of heme oxygenase-1 in hepatocytes.
PG  - 55
LID - 10.1186/1743-7075-11-55 [doi]
LID - 55
AB  - BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for liver 
      diseases, such as fatty liver and hepatic fibrosis. However, the mechanisms 
      underlying this pro-oxidative effect of homocysteine (Hcy) in hepatocytes remain 
      largely unknown. Thus, we investigated the effect of Hcy on the gene expression 
      of heme oxygenase-1 (HO-1), the primary rate-limiting enzyme in heme catabolism 
      and a key anti-oxidant detoxification enzyme in maintaining cellular redox 
      homeostasis. METHODS: In vivo, twenty male C57BL/6 mice at 8 weeks of age were 
      randomly divided into two groups. One group was fed a chow diet (chow group; 
      n = 10), the other group of mice was fed a methionine-supplemented diet (Met 
      group, 1 mg kg(-1) day(-1) L-methionine in drinking water; n = 10) for 4 weeks. 
      In vitro, HepG2 cells were stimulated with different doses of homocysteine (Hcy). 
      RESULTS: Four weeks' methionine supplementation caused a significant increase of 
      plasma Hcy concentration and a decrease of HO-1 expression in the liver of 
      C57BL/6 mice than mice received chow diet. Besides, SOD enzyme activities were 
      impaired and the level of oxidative stress markers, such as malondialdehyde (MDA) 
      were elevated in the liver from mice supplemented with methionine compared with 
      control mice. In cultured hepatocytes, Hcy treatment reduced both the mRNA and 
      protein levels of HO-1 dose-dependently. However, Hcy had no effect on the gene 
      expression of Nrf2, the major transcriptional regulator of HO-1. Instead, Hcy 
      induced the expression of Bach1, a transcriptional repressor of HO-1. In 
      addition, Hcy stimulated the nuclear localization of Bach1 but prevented that of 
      Nrf2. Furthermore, we found that knockdown of Bach1 attenuated the suppression of 
      the HO-1 expression by Hcy. CONCLUSIONS: Collectively, our results demonstrated 
      that Bach1 plays an important role in Hcy-triggered ROS generations through 
      inhibiting HO-1 expression, likely, resulting from the disturbed interplay 
      between Bach1 and Nrf2.
FAU - Luo, Xiaoqin
AU  - Luo X
AD  - Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, 
      Xi'an, 710061 China ; Department of Public Health, School of Medicine, Xi'an 
      Jiaotong University, Xi'an, 710061 China ; Nutrition and Food Safety Engineering 
      Research Center of Shaanxi Province, School of Medicine, Xi'an Jiaotong 
      University, Xi'an, 710061 China.
FAU - Xiao, Lei
AU  - Xiao L
AD  - Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, 
      Xi'an, 710061 China.
FAU - Yang, Haixia
AU  - Yang H
AD  - Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, 
      Xi'an, 710061 China ; Department of Public Health, School of Medicine, Xi'an 
      Jiaotong University, Xi'an, 710061 China ; Nutrition and Food Safety Engineering 
      Research Center of Shaanxi Province, School of Medicine, Xi'an Jiaotong 
      University, Xi'an, 710061 China.
FAU - Zhang, Ruijuan
AU  - Zhang R
AD  - Department of Public Health, School of Medicine, Xi'an Jiaotong University, 
      Xi'an, 710061 China ; Nutrition and Food Safety Engineering Research Center of 
      Shaanxi Province, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061 
      China.
FAU - Jiang, Manli
AU  - Jiang M
AD  - Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, 
      Xi'an, 710061 China.
FAU - Ni, Jiahua
AU  - Ni J
AD  - Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, 
      Xi'an, 710061 China.
FAU - Lei, Ting
AU  - Lei T
AD  - Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, 
      Xi'an, 710061 China.
FAU - Wang, Nanping
AU  - Wang N
AD  - Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, 
      Xi'an, 710061 China ; Institute of Cardiovascular Science, Peking University, 
      Beijing, 100191 China.
LA  - eng
PT  - Journal Article
DEP - 20141208
PL  - England
TA  - Nutr Metab (Lond)
JT  - Nutrition & metabolism
JID - 101231644
PMC - PMC4268895
OTO - NOTNLM
OT  - Bach1
OT  - Heme Oxygenase-1
OT  - Homocysteine
OT  - Nrf2
OT  - Reactive oxygen species
EDAT- 2014/12/19 06:00
MHDA- 2014/12/19 06:01
PMCR- 2014/12/08
CRDT- 2014/12/19 06:00
PHST- 2014/07/22 00:00 [received]
PHST- 2014/11/27 00:00 [accepted]
PHST- 2014/12/19 06:00 [entrez]
PHST- 2014/12/19 06:00 [pubmed]
PHST- 2014/12/19 06:01 [medline]
PHST- 2014/12/08 00:00 [pmc-release]
AID - 625 [pii]
AID - 10.1186/1743-7075-11-55 [doi]
PST - epublish
SO  - Nutr Metab (Lond). 2014 Dec 8;11(1):55. doi: 10.1186/1743-7075-11-55. eCollection 
      2014.