PMID- 33675119
OWN - NLM
STAT- MEDLINE
DCOM- 20210921
LR  - 20210921
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 25
IP  - 7
DP  - 2021 Apr
TI  - Hydrogen sulphide reduces hyperhomocysteinaemia-induced endothelial ER stress by 
      sulfhydrating protein disulphide isomerase to attenuate atherosclerosis.
PG  - 3437-3448
LID - 10.1111/jcmm.16423 [doi]
AB  - Hyperhomocysteinaemia (HHcy)-impaired endothelial dysfunction including 
      endoplasmic reticulum (ER) stress plays a crucial role in atherogenesis. Hydrogen 
      sulphide (H(2) S), a metabolic production of Hcy and gasotransmitter, exhibits 
      preventing cardiovascular damages induced by HHcy by reducing ER stress, but the 
      underlying mechanism is unclear. Here, we made an atherosclerosis with HHcy mice 
      model by ApoE knockout mice and feeding Pagien diet and drinking L-methionine 
      water. H(2) S donors NaHS and GYY4137 treatment lowered plaque area and ER stress 
      in this model. Protein disulphide isomerase (PDI), a modulation protein folding 
      key enzyme, was up-regulated in plaque and reduced by H(2) S treatment. In 
      cultured human aortic endothelial cells, Hcy dose and time dependently elevated 
      PDI expression, but inhibited its activity, and which were rescued by H(2) S. 
      H(2) S and its endogenous generation key enzyme-cystathionine gamma lyase induced a 
      new post-translational modification-sulfhydration of PDI. Sulfhydrated PDI 
      enhanced its activity, and two cysteine-terminal CXXC domain of PDI was 
      identified by site mutation. HHcy lowered PDI sulfhydration association ER 
      stress, and H(2) S rescued it but this effect was blocked by cysteine site 
      mutation. Conclusively, we demonstrated that H(2) S sulfhydrated PDI and enhanced 
      its activity, reducing HHcy-induced endothelial ER stress to attenuate 
      atherosclerosis development.
CI  - (c) 2021 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Jiang, Shan
AU  - Jiang S
AD  - Institute of Hypoxia Medicine, Wenzhou Medical University, Zhejiang, China.
FAU - Xu, Wenjing
AU  - Xu W
AD  - Department of Pathology, Xi'an Medical University, Shanxi, China.
FAU - Chen, Zhenzhen
AU  - Chen Z
AD  - State Key Laboratory of Cardiovascular Disease, Hypertension Center, National 
      Center for Cardiovascular Diseases, Fuwai Hospital of Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, China.
FAU - Cui, Changting
AU  - Cui C
AD  - State Key Laboratory of Cardiovascular Disease, Hypertension Center, National 
      Center for Cardiovascular Diseases, Fuwai Hospital of Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, China.
FAU - Fan, Xiaofang
AU  - Fan X
AD  - Institute of Hypoxia Medicine, Wenzhou Medical University, Zhejiang, China.
FAU - Cai, Jun
AU  - Cai J
AD  - State Key Laboratory of Cardiovascular Disease, Hypertension Center, National 
      Center for Cardiovascular Diseases, Fuwai Hospital of Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, China.
FAU - Gong, Yongsheng
AU  - Gong Y
AD  - Institute of Hypoxia Medicine, Wenzhou Medical University, Zhejiang, China.
FAU - Geng, Bin
AU  - Geng B
AUID- ORCID: 0000-0001-7573-8710
AD  - Institute of Hypoxia Medicine, Wenzhou Medical University, Zhejiang, China.
AD  - State Key Laboratory of Cardiovascular Disease, Hypertension Center, National 
      Center for Cardiovascular Diseases, Fuwai Hospital of Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, China.
LA  - eng
GR  - BJJWZYJH01201910023029/Beijing Outstanding Young Scientist Program/
GR  - 2020-12M-1-006/CAMS Innovation Fund for Medical Sciences/
GR  - 81670379/National Natural Science Foundation of China/
GR  - 81870318/National Natural Science Foundation of China/
GR  - 81630014/National Natural Science Foundation of China/
GR  - 81825002/National Natural Science Foundation of China/
GR  - 81800367/National Natural Science Foundation of China/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210306
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 5.3.4.1 (Protein Disulfide-Isomerases)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*metabolism
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Endothelial Cells/*metabolism
MH  - HEK293 Cells
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hydrogen Sulfide/*metabolism/*pharmacology
MH  - Hyperhomocysteinemia/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout, ApoE
MH  - Protein Disulfide-Isomerases/chemistry/*metabolism
MH  - Up-Regulation
PMC - PMC8034471
OTO - NOTNLM
OT  - atherosclerosis
OT  - endoplasmic reticulum stress
OT  - homocysteine
OT  - hydrogen sulphide
OT  - protein disulphide isomerase
OT  - sulfhydration
COIS- The authors confirm that there are no conflicts of interest.
EDAT- 2021/03/07 06:00
MHDA- 2021/09/22 06:00
PMCR- 2021/04/01
CRDT- 2021/03/06 05:45
PHST- 2021/02/16 00:00 [revised]
PHST- 2020/05/05 00:00 [received]
PHST- 2021/02/18 00:00 [accepted]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/09/22 06:00 [medline]
PHST- 2021/03/06 05:45 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - JCMM16423 [pii]
AID - 10.1111/jcmm.16423 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2021 Apr;25(7):3437-3448. doi: 10.1111/jcmm.16423. Epub 2021 Mar 
      6.