Abstract 15292: Bradykinin Increases Cytosolic Ca2+ by Activating IP3Rs and TRPC1 Channels in Human Cardiac C-kit+ Progenitor Cells
Introduction: Bradykinin is an endogenous protective peptide. In a previous study we demonstrated that bradykinin regulates cell proliferation and migration by activating B2Rs and pAkt/pERK1/2 signals in human c-kit+ cardiac progenitor cells.
Hypothesis: The regulation of proliferation and migration by bradykinin may be mediated by increasing intracellular Ca2+ (Ca2+i) activity in human c-kit+ cardiac progenitor cells.
Methods: Confocal microscopy was used to examine Ca2+i level, and the related molecular biological approaches were employed to determine the molecular signaling pathways involving in BK-induced regulation of cell proliferation and migration in cultured human c-kit+ cardiac progenitor cells.
Results: Bradykinin induced a significant Ca2+i transient followed by a sustained Ca2+i increase in human cardiac c-kit+ progenitor cells. Both Ca2+i transient and sustained Ca2+i increase were aborted by IP3Rs blocker araguspongin B, silencing IP3Rs or the PKC inhibitor chelerythrine. Interestingly, the sustained Ca2+i increase was reduced by the TRPC channel blockers La3+ and SKF-96365 or silencing TRPC1 channels. In addition, bradykinin-induced increase of cell proliferation and mobility were decreased in cells with silencing IP3Rs, and partially reduced by silencing TRPC1 channels. Moreover, bradykinin-induced increase of pAkt and pERK1/2 as well as cyclin D1 was also reduced by chelerythrine or silencing IP3Rs or TRPC1 channels.
Conclusions: These results demonstrate for the first time that bradykinin-mediated Ca2+i transient and sustained Ca2+i increase is involved in activating IP3Rs followed by eliciting PKC and TRPC1, which participate in regulating cell proliferation and mobility via increasing pAkt and pERK1/2 in human cardiac c-kit+ progenitor cells.
Author Disclosures: G. Li: None. W. Wu: None. L. Jie: None. Y. Wang: None. G. Li: None.
- © 2016 by American Heart Association, Inc.