title: Inhibition of Ca2+-release-activated Ca2+ channel (CRAC) and K+ channels by curcumin in Jurkat-T cells.
abstract: The increase in cytoplasmic Ca(2+) concentration (Δ[Ca(2+)](c)) mediated by the Ca(2+)-release-activated Ca(2+) channel (CRAC) is a critical signal for the activation of lymphocytes. Also, the voltage-gated K(+) channel (K(v)) and intermediate-conductance Ca(2+)-activated K(+) channel (IKCa1/SK4) have drawn attention as pharmacological targets for regulating immune responses. Since polyphenolic agents have various immunomodulatory effects, here we compared the effects of curcumin, rosmarinic acid, resveratrol, and epigallocatechin gallate on the ionic currents through CRAC (I(CRAC)), K(v) (I(Kv)), SK4 (I(SK4)) and on the Δ[Ca(2+)](c) of Jurkat-T cells using the patch clamp technique and fura-2 spectrofluorimetry. Curcumin (10 µM) inhibited store-operated Ca(2+) entry (SOCE). Consistently, dose-dependent inhibition of I(CRAC) by curcumin was confirmed in Jurkat-T (IC(50), 5.9 µM) and the HEK293 cells overexpressing Orai1 and STIM1 (IC(50), 0.6 µM). Also, curcumin inhibited both I(Kv) (IC(50), 11.9 µM) and I(SK4) (IC(50), 4.2 µM). The other polyphenols (rosmarinic acid, resveratrol, and epigallocatechin gallate at 10 - 30 µM) had no effect on SOCE and showed only a partial inhibition of the K(+) currents. In summary, among the tested polyphenolic agents, curcumin showed prominent inhibition of major ion channels in lymphocytes, which might contribute to the anti-inflammatory effects of curcumin. [Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.10209FP].
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Shin
authors.forename: Eun Yeong
authors.initials: EY
authors.lastname: Seo
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Nam
authors.forename: Hyang Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Kim
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071740:ORAI1 Protein; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D059808:Polyphenols; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005419:Flavonoids; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D010636:Phenols; D059808:Polyphenols; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D003474:Curcumin; D002118:Calcium