PMID- 25925287
OWN - NLM
STAT- MEDLINE
DCOM- 20160209
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 36
IP  - 1
DP  - 2015
TI  - Chloroquine Inhibits Ca(2+) Signaling in Murine CD4(+) Thymocytes.
PG  - 133-40
LID - 10.1159/000374058 [doi]
AB  - BACKGROUND/AIMS: Bitter-tasting chloroquine can suppress T cell activation by 
      inhibiting Ca(2+) signaling. However, the mechanism of inhibition remains largely 
      unclear. METHODS: In this study, CD4(+) T cells were isolated from the thymus, 
      and the calcium content of CD4(+) thymocytes was measured using fura-2 AM and a 
      TILL imaging system. Pyrazole-3 (Pyr3), thapsigargin (TG), and caffeine were used 
      to assess the effects of chloroquine on the intracellular Ca(2+) content of 
      CD4(+) T cells. RESULTS: In murine CD4(+) thymocytes, chloroquine decreased the 
      TG-triggered intracellular Ca(2+) increase in a dose-dependent manner. In the 
      absence of chloroquine under Ca(2+)-free conditions (0 mM Ca(2+) and 0.5 mM 
      EGTA), TG induced a transient Ca(2+) increase. After restoration of the 
      extracellular Ca(2+) concentration to 2 mM, a dramatic Ca(2+) increase occurred. 
      This elevation was completely blocked by chloroquine and was markedly inhibited 
      by Pyr3, a selective antagonist of transient receptor potential C3 (TRPC3) 
      channel and stromal interaction molecule (STIM)/Orai channel. Furthermore, the 
      TG-induced transient Ca(2+) increase under Ca(2+)-free conditions was eliminated 
      in the presence of chloroquine. Chloroquine also blocked the dialyzed 
      inositol-1,4,5-trisphosphate (IP3)-induced intracellular Ca(2+) increase. 
      However, chloroquine was not able to decrease the caffeine-induced Ca(2+) 
      increase. CONCLUSION: These data indicate that chloroquine inhibits the elevation 
      of intracellular Ca(2+) in thymic CD4(+) T cells by inhibiting IP3 
      receptor-mediated Ca(2+) release from intracellular stores and TRPC3 
      channel-mediated and/or STIM/Orai channel-mediated Ca(2+) influx.
FAU - Xu, Jin-Chao
AU  - Xu JC
AD  - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection 
      and Application of Special Plants in the Wuling Area of China, College of Life 
      Sciences, South-Central University for Nationalities, Wuhan, China.
FAU - Peng, Yong-Bo
AU  - Peng YB
FAU - Wei, Ming-Yu
AU  - Wei MY
FAU - Wu, Yi-Fan
AU  - Wu YF
FAU - Guo, Donglin
AU  - Guo D
FAU - Qin, Gangjian
AU  - Qin G
FAU - Ji, Guangju
AU  - Ji G
FAU - Shen, Jinhua
AU  - Shen J
FAU - Liu, Qing-Hua
AU  - Liu QH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150427
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Pyrazoles)
RN  - 0 
      (ethyl-1-(4-(2*3*3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate)
RN  - 3G6A5W338E (Caffeine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 886U3H6UFF (Chloroquine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*drug effects/metabolism
MH  - Caffeine/pharmacology
MH  - Calcium/*metabolism
MH  - Calcium Signaling/*drug effects
MH  - Cells, Cultured
MH  - Chloroquine/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Mice
MH  - Pyrazoles/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Thymocytes/cytology/*drug effects/metabolism
EDAT- 2015/05/01 06:00
MHDA- 2016/02/10 06:00
CRDT- 2015/05/01 06:00
PHST- 2015/03/17 00:00 [accepted]
PHST- 2015/05/01 06:00 [entrez]
PHST- 2015/05/01 06:00 [pubmed]
PHST- 2016/02/10 06:00 [medline]
AID - 000374058 [pii]
AID - 10.1159/000374058 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2015;36(1):133-40. doi: 10.1159/000374058. Epub 2015 Apr 
      27.