PMID- 29102635
OWN - NLM
STAT- MEDLINE
DCOM- 20180705
LR  - 20181010
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 113
DP  - 2017 Dec
TI  - Nitration-mediated deficiency of cystathionine beta-synthase activity accelerates 
      the progression of hyperhomocysteinemia.
PG  - 519-529
LID - S0891-5849(17)31172-3 [pii]
LID - 10.1016/j.freeradbiomed.2017.10.389 [doi]
AB  - Deficiency of cystathionine beta-synthase (CBS) activity is the most common cause of 
      increased homocysteine (Hcy). However, until now the underlying mechanisms why 
      CBS activity decreased still remain unresolved. The goal of this study was to 
      explore the contribution of nitrative stress to deficiency of CBS activity, and 
      further identify the possible nitration sites of CBS protein. Results showed that 
      in elderly people, there was an increased nitrative stress level, which was 
      relative to elevated Hcy level. In natural aging rats and diet-induced 
      hyperhomocysteinemia (HHcy) rats, the levels of Hcy and nitrative stress were 
      both elevated, and interestingly, pretreatment with peroxynitrite (ONOO(-)) 
      scavenger FeTMPyP ameliorated the elevation of Hcy as well as nitrative stress. 
      Further experiments showed the reduction of CBS bioactivity and elevation of CBS 
      nitration in two rats models were both reversed by FeTMPyP pretreatment. In 
      vitro, replacement of tyrosine (Tyr, Y) residue (Tyr(163), Tyr(223), Tyr(381), 
      Tyr(518)) in CBS with alanine (Ala, A) abolished the Hcy-mediated CBS 
      inactivation. These results highlighted that deficiency of CBS activity was 
      correlated with the nitration of CBS at Tyr(163), Tyr(223), Tyr(381) and 
      Tyr(518), which may play a mutual role in the progression of HHcy. This discovery 
      may shed a novel light on the pathogenesis of HHcy and provide a possible gene 
      therapy target to HHcy.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Wang, Huanyuan
AU  - Wang H
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Department of Traditional 
      Chinese Medicine, Peking Union Medical College Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing 100730, China.
FAU - Sun, Qi
AU  - Sun Q
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China.
FAU - Zhou, Yi
AU  - Zhou Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China.
FAU - Luo, Chenghua
AU  - Luo C
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China.
FAU - Xu, Jiahui
AU  - Xu J
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China.
FAU - Dong, Yu
AU  - Dong Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China.
FAU - Wu, Ye
AU  - Wu Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China.
FAU - Liu, Huirong
AU  - Liu H
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China.
FAU - Wang, Wen
AU  - Wang W
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of 
      Metabolic Disorders Related Cardiovascular Diseases, Beijing 100069, China. 
      Electronic address: wangwen@ccmu.edu.cn.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171105
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III))
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Metalloporphyrins)
RN  - 0 (Nitro Compounds)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Cystathionine beta-Synthase/*deficiency/genetics
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Female
MH  - Free Radical Scavengers/pharmacology
MH  - Homocysteine/*metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/drug therapy/genetics/*metabolism/pathology
MH  - Male
MH  - Metalloporphyrins/pharmacology
MH  - Middle Aged
MH  - Mutation
MH  - Nitro Compounds/*metabolism
MH  - *Nitrosative Stress
MH  - *Protein Processing, Post-Translational
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Tyrosine/metabolism
OTO - NOTNLM
OT  - Aging
OT  - Cystathionine beta-synthase
OT  - Homocysteine
OT  - Hyperhomocysteinemia
OT  - Nitration
OT  - Nitrative stress
EDAT- 2017/11/06 06:00
MHDA- 2018/07/06 06:00
CRDT- 2017/11/06 06:00
PHST- 2017/06/10 00:00 [received]
PHST- 2017/10/08 00:00 [revised]
PHST- 2017/10/31 00:00 [accepted]
PHST- 2017/11/06 06:00 [pubmed]
PHST- 2018/07/06 06:00 [medline]
PHST- 2017/11/06 06:00 [entrez]
AID - S0891-5849(17)31172-3 [pii]
AID - 10.1016/j.freeradbiomed.2017.10.389 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2017 Dec;113:519-529. doi: 
      10.1016/j.freeradbiomed.2017.10.389. Epub 2017 Nov 5.