PMID- 29654766
OWN - NLM
STAT- MEDLINE
DCOM- 20180919
LR  - 20180919
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 500
IP  - 2
DP  - 2018 Jun 2
TI  - Orai1 downregulation impairs lymphocyte function in type 2 diabetes mellitus.
PG  - 384-390
LID - S0006-291X(18)30852-0 [pii]
LID - 10.1016/j.bbrc.2018.04.083 [doi]
AB  - BACKGROUND/AIMS: It has been suggested that diabetes is associated with immune 
      dysfunction, in which Ca(2+) signaling malfunction in lymphocyte may contributes 
      most. However, the pattern of the Ca(2+) signal disorder and the mechanism(s) 
      that explains the change are unclear. Here, in this study we aimed to investigate 
      possible changes and mechanism(s) accounting for the internal Ca(2+) signals in 
      diabetic T lymphocyte upon stimulation. METHODS AND RESULTS: Using Fura-2-AM, we 
      found a significant decrease in Ca(2+) influx induced by thapsigargin (TG) and 
      anti-CD3 antibody (OKT3) in T lymphocytes from blood of both diabetes patients 
      and animals. Furthermore, a downregulated Orai1 protein expression, but not mRNA, 
      was also observed in these cells using western blot and qRT-PCR, respectively. In 
      addition, in high-glucose and agonist treated Jurkat T cells, Ca(2+) entry and 
      the release of interleukin-2 (IL-2) were also decreased. Orai1 expression 
      reduced, while stromal interaction molecule 1 (STIM1) and other downstream 
      proteins remained unchanged. CONCLUSION: This study demonstrates that the 
      declined Orai1 expression, at least partly, contributes to the downregulated 
      Ca(2+) entry during lymphocyte excitation, providing an important mechanism for T 
      lymphocyte malfunction in diabetes.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Wang, Haoyang
AU  - Wang H
AD  - Department of Pharmacology, Beijing Key Laboratory of Metabolic Disturbance 
      Related Cardiovascular Disease, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, PR China.
FAU - Wang, Cong
AU  - Wang C
AD  - Department of Pharmacology, Beijing Key Laboratory of Metabolic Disturbance 
      Related Cardiovascular Disease, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, PR China.
FAU - Wang, Limin
AU  - Wang L
AD  - Department of Pharmacology, Beijing Key Laboratory of Metabolic Disturbance 
      Related Cardiovascular Disease, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, PR China.
FAU - Liu, Tiantian
AU  - Liu T
AD  - Department of Pharmacology, Beijing Key Laboratory of Metabolic Disturbance 
      Related Cardiovascular Disease, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, PR China.
FAU - Wang, Zhiqiang
AU  - Wang Z
AD  - Department of Pharmacology, Beijing Key Laboratory of Metabolic Disturbance 
      Related Cardiovascular Disease, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, PR China.
FAU - You, Hongjie
AU  - You H
AD  - Department of Pharmacology, Beijing Key Laboratory of Metabolic Disturbance 
      Related Cardiovascular Disease, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, PR China.
FAU - Zheng, Yuanyuan
AU  - Zheng Y
AD  - Department of Pharmacology, Beijing Key Laboratory of Metabolic Disturbance 
      Related Cardiovascular Disease, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, PR China.
FAU - Luo, Dali
AU  - Luo D
AD  - Department of Pharmacology, Beijing Key Laboratory of Metabolic Disturbance 
      Related Cardiovascular Disease, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, PR China. Electronic address: luodl@ccmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180417
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (ORAI1 Protein)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Type 2/blood/*metabolism
MH  - *Down-Regulation/drug effects
MH  - Glucose/toxicity
MH  - Humans
MH  - Lymphocytes/drug effects/*metabolism
MH  - Mice, Inbred C57BL
MH  - ORAI1 Protein/*metabolism
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Diabetes mellitus
OT  - Immune dysfunction
OT  - Orai1
OT  - Store-operated Ca(2+) entry
EDAT- 2018/04/15 06:00
MHDA- 2018/09/20 06:00
CRDT- 2018/04/15 06:00
PHST- 2018/04/09 00:00 [received]
PHST- 2018/04/11 00:00 [accepted]
PHST- 2018/04/15 06:00 [pubmed]
PHST- 2018/09/20 06:00 [medline]
PHST- 2018/04/15 06:00 [entrez]
AID - S0006-291X(18)30852-0 [pii]
AID - 10.1016/j.bbrc.2018.04.083 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Jun 2;500(2):384-390. doi: 
      10.1016/j.bbrc.2018.04.083. Epub 2018 Apr 17.