title: Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Qiu-yue
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Qiqihaer Medical College, Qiqihaer 160001, China.
authors.forename: Ming-rui
authors.initials: MR
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Chun-li
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Department of Rheumatology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Du
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Jing-ya
authors.initials: JY
authors.lastname: Zeng
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Hai-liang
authors.initials: HL
authors.lastname: Bi
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: syh200415@126.com.
authors.forename: Yi-hua
authors.initials: YH
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000378:metabolism*; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D044169:Receptors, Calcium-Sensing; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C492145:Trpc6 protein, rat; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases
keywords: Calcium-sensing receptor; Cytokine; Lymphocytes; Sepsis; Transient receptor potential channel