title: Identification of a Calcium Signalling Pathway of S-[6]-Gingerol in HuH-7 Cells.
abstract: Calcium signals in hepatocytes control cell growth, proliferation, and death. Members of the transient receptor potential (TRP) cation channel superfamily are candidate calcium influx channels. NF κ B activation strictly depends on calcium influx and often induces antiapoptotic genes favouring cell survival. Previously, we reported that S-[6]-gingerol is an efficacious agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in neurones. In this study, we tested the effect of S-[6]-gingerol on HuH-7 cells using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and luciferase measurements. We found that S-[6]-gingerol induced a transient rise in [Ca(2+)] i in HuH-7 cells. The increase in [Ca(2+)] i induced by S-[6]-gingerol was abolished by preincubation with EGTA and was also inhibited by the TRPV1 channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed by mRNA analysis as well as a test for increase of [Ca(2+)] i by TRPV1 agonist capsaicin and its inhibition by capsazepine. We found that S-[6]-gingerol induced rapid NF κ B activation through TRPV1 in HuH-7 cells. Furthermore, S-[6]-gingerol-induced NF κ B activation was dependent on the calcium gradient and TRPV1. The rapid NF κ B activation by S-[6]-gingerol was associated with an increase in mRNA levels of NF κ B-target genes: cIAP-2, XIAP, and Bcl-2 that encode antiapoptotic proteins.
authors: Faculty of Pharmacy, University of Sydney, Camperdown, NSW 2006, Australia ; Heart Research Institute, Newtown, NSW 2042, Australia ; Department of Endocrinology, Dezhou People's Hospital, Dezhou, Shandong 253014, China.
authors: Xiao-Hong
authors: XH
authors: Li
authors: Kristine C Y
authors: KC
authors: McGrath
authors: Van H
authors: VH
authors: Tran
authors: Yi-Ming
authors: YM
authors: Li
authors: Sravan
authors: S
authors: Mandadi
authors: Colin C
authors: CC
authors: Duke
authors: Alison K
authors: AK
authors: Heather
authors: Basil D
authors: BD
authors: Roufogalis
references: Genes Dev. 1999 Feb 1;13(3):239-52
references: 9990849
references: J Cell Sci. 2002 Aug 1;115(Pt 15):3181-91
references: 12118073
references: J Neurosci Res. 2009 Feb;87(2):482-94
references: 18752301
references: Nat Immunol. 2002 Mar;3(3):221-7
references: 11875461
references: Nature. 1997 Oct 23;389(6653):816-24
references: 9349813
references: Cardiovasc Res. 2011 Dec 1;92(3):504-13
references: 21908651
references: Trends Cell Biol. 2005 Oct;15(10):555-63
references: 16150595
references: Nat Rev Cancer. 2002 Sep;2(9):647-56
references: 12209154
references: Oncogene. 2005 Apr 7;24(15):2558-67
references: 15735738
references: J Ethnopharmacol. 1989 Nov;27(1-2):129-40
references: 2615416
references: J Surg Res. 2007 Apr;138(2):209-13
references: 17291534
references: J Biol Chem. 2003 Oct 10;278(41):39615-24
references: 12896980
references: Cancer Res. 1998 Dec 1;58(23):5315-20
references: 9850056
references: J Mol Endocrinol. 2000 Oct;25(2):169-93
references: 11013345
references: Biochem Biophys Res Commun. 2009 Apr 24;382(1):134-9
references: 19268427
references: Science. 1998 Aug 28;281(5381):1322-6
references: 9735050
references: Med J Aust. 2006 Aug 21;185(S4):S1-S24
references: 17022438
references: J Biol Chem. 2007 Feb 9;282(6):4210-7
references: 17158097
references: Free Radic Res. 2007 May;41(5):603-14
references: 17454143
references: Br J Pharmacol. 2002 Nov;137(6):793-8
references: 12411409
references: J Nat Prod. 2008 Jan;71(1):137-40
references: 18181576
references: J Pharmacol Exp Ther. 2005 Jun;313(3):1305-13
references: 15764738
references: Planta Med. 2012 Sep;78(14):1549-55
references: 22828920
references: Dig Dis Sci. 2006 Jun;51(6):1087-102
references: 16865576
references: Basic Clin Pharmacol Toxicol. 2012 Mar;110(3):238-44
references: 21902812
references: J Biochem Mol Biol. 2002 Jan 31;35(1):28-40
references: 16248967
references: Chem Pharm Bull (Tokyo). 1982 Feb;30(2):754-7
references: 7094159
references: Zhongguo Zhong Yao Za Zhi. 2005 Oct;30(20):1569-73
references: 16422532
references: Biofactors. 2004;21(1-4):27-31
references: 15630166
references: J Med Chem. 1993 Aug 6;36(16):2362-72
references: 8360881
references: Biochim Biophys Acta. 2008 May;1783(5):651-72
references: 18291110