PMID- 25467798 OWN - NLM STAT- MEDLINE DCOM- 20150304 LR - 20150102 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 64 IP - 1 DP - 2015 Mar TI - Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis. PG - 18-25 LID - S0161-5890(14)00283-1 [pii] LID - 10.1016/j.molimm.2014.10.018 [doi] AB - Sepsis is a systemic inflammatory response syndrome induced by infection. T Lymphocytes play an important role in this disease. Transient receptor potential (TRP) channels and calcium-sensing receptors (CaSR) are expressed in lymphocytes to promote intracellular Ca(2+) release. However, data about the link between CaSR and TRP channels in septic T lymphocytes are few. In this study, by Ca(2+) imaging and Western blotting, we found that in septic rat peripheral blood T lymphocytes expressions of TRPC3 and TRPC6 proteins are higher. The SR/ER Ca(2+) ATPase inhibitor thapsigargin (TG) and CaSR agonist NPS R-568 also increased expressions of TRPC3 and TRPC6 proteins, which were reversed by PLC-IP3 channel blocker U73122 and TRPC channels inhibitor SKF96365. By Ca(2+) imaging, we found that the depletion of ER Ca(2+) stores by TG elicited a transient rise in cytoplasmic Ca(2+), followed by sustained increase depending on extracellular Ca(2+). But, SKF96365, not Verapamil (L-type channels inhibitor) and NiCl2 (Na(+)/Ca(2+) exchanger inhibitor), inhibited the relatively high [Ca(2+)]i. NPS R-568 also resulted in the same effect, and the duration of [Ca(2+)]i increase was eliminated completely by U73122 and was reduced in the absence of [Ca(2+)]o. NPS R-568 and TG increased the apoptotic ratio of septic T lymphocytes, which can be suppressed by SKF96365 and U73122. These results suggested that CaSR activation promoted the expression of TRPC3 and TRPC6 and enhanced T lymphocytes apoptosis through PLC-IP3 signaling pathway in sepsis. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Wu, Qiu-yue AU - Wu QY AD - Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Sun, Ming-rui AU - Sun MR AD - Department of Pharmacology, Qiqihaer Medical College, Qiqihaer 160001, China. FAU - Wu, Chun-li AU - Wu CL AD - Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Li, Yang AU - Li Y AD - Department of Rheumatology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Du, Jing-jing AU - Du JJ AD - Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Zeng, Jing-ya AU - Zeng JY AD - Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Bi, Hai-liang AU - Bi HL AD - Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Sun, Yi-hua AU - Sun YH AD - Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: syh200415@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141112 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Receptors, Calcium-Sensing) RN - 0 (TRPC Cation Channels) RN - 0 (TRPC3 cation channel) RN - 0 (Trpc6 protein, rat) RN - 67526-95-8 (Thapsigargin) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - EC 3.1.4.- (Type C Phospholipases) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Calcium Signaling/drug effects MH - Extracellular Space/drug effects/metabolism MH - Flow Cytometry MH - Inositol 1,4,5-Trisphosphate/metabolism MH - Intracellular Space/drug effects/metabolism MH - Ion Channel Gating/drug effects MH - Rats, Wistar MH - Receptors, Calcium-Sensing/agonists/*metabolism MH - Sepsis/blood/*immunology/*pathology MH - T-Lymphocytes/cytology/drug effects/*metabolism MH - TRPC Cation Channels/*metabolism MH - Thapsigargin/pharmacology MH - Type C Phospholipases/metabolism OTO - NOTNLM OT - Calcium-sensing receptor OT - Cytokine OT - Lymphocytes OT - Sepsis OT - Transient receptor potential channel EDAT- 2014/12/04 06:00 MHDA- 2015/03/05 06:00 CRDT- 2014/12/04 06:00 PHST- 2014/09/19 00:00 [received] PHST- 2014/10/23 00:00 [accepted] PHST- 2014/12/04 06:00 [entrez] PHST- 2014/12/04 06:00 [pubmed] PHST- 2015/03/05 06:00 [medline] AID - S0161-5890(14)00283-1 [pii] AID - 10.1016/j.molimm.2014.10.018 [doi] PST - ppublish SO - Mol Immunol. 2015 Mar;64(1):18-25. doi: 10.1016/j.molimm.2014.10.018. Epub 2014 Nov 12.