Tabriz University of Medical Sciences BioImpacts 2228-5652 14 2 2024 03 01 Essential role of CD38 in platelet aggregation through the PKC- mediated internalization and activation 27780 27780 10.34172/bi.2023.27780 EN Mazhar Mushtaq https://orcid.org/0000-0002-2126-924X Maira Mahmood https://orcid.org/0000-0002-0459-2598 Uzma Jabbar https://orcid.org/0000-0003-4078-2636 Uh-Hyun Kim https://orcid.org/0000-0003-3304-7190 Journal Article 10.34172/bi.2023.27780 2023 01 22 2023 07 26 Introduction: CD38 is a multifunctional enzyme with a potent Ca2+ mobilizing effect, cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP). Here, we aimed to demonstrate the role of CD38 in platelets via protein kinase C (PKC)-mediated internalization and activation. Methods: Mouse platelets were used in this study. Thrombin, an agonist of platelet function, provoked a prompt and long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i), resulting from an interplay of multifold Ca2+ mobilizing messengers.The signaling pathway was delineated using different inhibitors and techniques such as platelet aggregation assay, intracellular calcium measurements, immunoprecipitation, immunoblotting, and flow cytometry. Results: We observed a sequential formation of cADPR and NAADP through CD38 activation by PKC of non-muscle myosin heavy chain IIA (MHCIIA), resulting in phospholipase C (PLC) activation in the thrombin-stimulated platelets. These findings reveal that PKC is fundamental in activating CD38 and elicits a physiological response in the murine platelets. Conclusion: PKC is involved in many signaling pathways. Specifically, PKC is involved in the internalization of CD38 via MHCIIA in CD38+/+ wild-type (WT) and CD38-/- knockout mice (KO). CD38 generates calcium-mobilizing agents that act on specific receptors of the calcium stores. Calcium triggered platelet aggregation while serving as a secondary messenger.