PMID- 29567540
OWN - NLM
STAT- MEDLINE
DCOM- 20181011
LR  - 20181011
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 102
DP  - 2018 Jun
TI  - Silencing ZAP70 prevents HSP65-induced reverse cholesterol transport and NF-kappaB 
      activation in T cells.
PG  - 271-277
LID - S0753-3322(17)36204-2 [pii]
LID - 10.1016/j.biopha.2018.03.082 [doi]
AB  - T cell activation by antigens binding to the T cell receptor (TCR) must be 
      properly regulated to ensure normal T cell development. The zeta chain-associated 
      70-kDa protein (ZAP70) is sequentially activated in response to TCR engagement 
      and serves as a critical component of the TCR signaling pathway, which is 
      essential for T cell activation. However, some roles of ZAP70 have not been fully 
      elucidated. In the present study, we analyzed the effects of ZAP70 on the 
      cholesterol efflux rate, nuclear factor kappaB (NF-kappaB) activation and cell 
      proliferation in T cells. Our study showed that silencing ZAP70 increased the 
      cholesterol efflux rate in T cells. We also found that silencing ZAP enhanced the 
      expression of ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette 
      transporter G1 (ABCG1), scavenger receptor-BI (SR-BI) peroxisome 
      proliferator-activated receptor-gamma (PPAR-gamma) and liver X receptor-alpha 
      (LXR-alpha). In contrast, the phosphorylation of ZAP70 by HSP65 decreased the 
      cholesterol efflux rate and the expression of five cholesterol transport proteins 
      in T cells. The phosphorylation of ZAP70 activated the downstream NF-kappaB signaling 
      pathway, which is involved in both T cell growth and function. Furthermore, 
      silencing ZAP70 inhibited T cell proliferation. These results indicate a crucial 
      and unexpected role for ZAP70 in the physiological activities of T cells, 
      suggesting that inhibition of ZAP70 is beneficial for anti-atherosclerosis.
CI  - Copyright (c) 2018. Published by Elsevier Masson SAS.
FAU - Hu, Jing
AU  - Hu J
AD  - Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern 
      Medical University, Guangzhou 510515, China. Electronic address: 
      619063676@qq.com.
FAU - Luo, Tiantian
AU  - Luo T
AD  - Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern 
      Medical University, Guangzhou 510515, China.
FAU - Xi, Dan
AU  - Xi D
AD  - Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern 
      Medical University, Guangzhou 510515, China.
FAU - Guo, Kai
AU  - Guo K
AD  - Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern 
      Medical University, Guangzhou 510515, China.
FAU - Hu, Lu
AU  - Hu L
AD  - Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern 
      Medical University, Guangzhou 510515, China.
FAU - Zhao, Jinzhen
AU  - Zhao J
AD  - Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern 
      Medical University, Guangzhou 510515, China.
FAU - Chen, Si
AU  - Chen S
AD  - Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern 
      Medical University, Guangzhou 510515, China.
FAU - Guo, Zhigang
AU  - Guo Z
AD  - Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern 
      Medical University, Guangzhou 510515, China. Electronic address: 
      guozhigang126@126.com.
LA  - eng
PT  - Journal Article
DEP - 20180322
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (heat-shock protein 65, human)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
RN  - EC 2.7.10.2 (ZAP70 protein, human)
SB  - IM
MH  - Biological Transport
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cholesterol/*metabolism
MH  - Gene Silencing
MH  - Heat-Shock Proteins/pharmacology/*physiology
MH  - Humans
MH  - Jurkat Cells
MH  - NF-kappa B/*immunology
MH  - Phosphorylation
MH  - RNA, Small Interfering/genetics
MH  - T-Lymphocytes/drug effects/*immunology/metabolism
MH  - Transfection
MH  - ZAP-70 Protein-Tyrosine Kinase/genetics/*physiology
OTO - NOTNLM
OT  - Inflammation
OT  - NF-kappaB
OT  - Reverse cholesterol transport
OT  - T cells
OT  - ZAP70
EDAT- 2018/03/24 06:00
MHDA- 2018/10/12 06:00
CRDT- 2018/03/24 06:00
PHST- 2017/11/18 00:00 [received]
PHST- 2018/03/14 00:00 [revised]
PHST- 2018/03/14 00:00 [accepted]
PHST- 2018/03/24 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2018/03/24 06:00 [entrez]
AID - S0753-3322(17)36204-2 [pii]
AID - 10.1016/j.biopha.2018.03.082 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2018 Jun;102:271-277. doi: 10.1016/j.biopha.2018.03.082. 
      Epub 2018 Mar 22.