Taurine inhibits myocardial fibrosis via PKCα and iNOS signaling pathways

Abstract

Although, taurine has demonstrated the important role in inhibiting proliferation of myofibroblasts (myoFb) and reversing cardiac remodeling, the underlying mechanisms remains largely unknown. Therefore, the present study is designed to shed light on this issue through exploring the signal pathways. The proliferation and cycle distribution of cultured myoFb were measured by MTT and flow cytometry assay, nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity were determined by nitrate reductase method and spectrophotometry. Subcellular distribution of phosphorylated protein kinase C-alpha (p-PKCa in the cytoplasmic membrane and iNOS in the cytoplasm of myoFb were analyzed by immunocytochemical and immunofluorescence staining. Protein levels of p-PKCa and iNOS were examined by Western blot. The data showed that taurine could significantly inhibit proliferation of myoFb and increase activities of iNOS and content of NO. Meanwhile, taurine abolished translocation of p-PKCa from cytosol to membrane and decreased protein expression of p-PKCa whereas, increased protein expression of iNOS after taurine treatment compared with AngII group. Furthermore, we elucidated relationship between p-PKCa and iNOS in signal transduction pathways using p-PKCa inhibitor L-threo-Dihydro-sphingosine (D4681) and iNOS inhibitor aminoguanidine (AG). Finally, these results showed p-PKCaprotein expression and membrane translocation were suppressed in D4681 and taurine group with no changes in AG and taurine group. Protein expression and activity of iNOS were both upregulated in D4681 and taurine group, but down regulated in AG and taurine group compared with taurine group. Together, these results suggest taurine inhibits proliferation of myoFb and reverses cardiac remodeling via PKCa and iNOS intracellular signal transduction pathways. Key words: Taurine, myocardial fibrosis, proliferation, signal transduction, cardiac remodeling.