Investigating the interplay between sarcosine and Ca2+-dependent signaling in prostate cells

Abstract

It has been shown that sarcosine supplementation stimulates proliferation and invassivenes of prostate cells. Nevertheless, the exact molecular mechanism responsible for this phenomenon is not known. In the present study we demonstrate that sarcosine increases expression of calmodulin (CaM), an important intracellular signaling molecule. Through this, sarcosine activates calmodulin-dependent protein kinases signaling. Pathway of activation CaM-dependent protein kinases can activate regulation of mitosis, proliferation, cell death, gene transcription and phosphorylation/ dephosphorlation of proteins. This is done through CaM binding of four Ca2+ ions. Interestingly, in this study, we identified decrese in free Ca2+ correlating with sarcosine-induced up-regulation of CaM. The influence of CaM to cell cycle changes was further verified using post transcritrional gene silencing using CaM-siRNA complex. Co-treatment of prostate cells with CaM-siRNA and sarcosine showed decrease in CaM-dependent kinases and cell invasiveness compared to sarcosine treatment only.It has been shown that sarcosine supplementation stimulates proliferation and invassivenes of prostate cells. Nevertheless, the exact molecular mechanism responsible for this phenomenon is not known. In the present study we demonstrate that sarcosine increases expression of calmodulin (CaM), an important intracellular signaling molecule. Through this, sarcosine activates calmodulin-dependent protein kinases signaling. Pathway of activation CaM-dependent protein kinases can activate regulation of mitosis, proliferation, cell death, gene transcription and phosphorylation/ dephosphorlation of proteins. This is done through CaM binding of four Ca2+ ions. Interestingly, in this study, we identified decrese in free Ca2+ correlating with sarcosine-induced up-regulation of CaM. The influence of CaM to cell cycle changes was further verified using post transcritrional gene silencing using CaM-siRNA complex. Co-treatment of prostate cells with CaM-siRNA and sarcosine showed decrease in CaM-dependent kinases and cell invasiveness compared to sarcosine treatment only.