OpiCa1 Modulates Cardiomyocyte Viability Through PI3K/Akt Inhibition with Minimal Systemic Impact Beyond RyR Targeting.

ABSTRACT: Calcins represent a class of novel peptide ligands for ryanodine receptors (RyRs), demonstrating therapeutic potential against Ca²⁺ dysregulation-related cardiac diseases. Nevertheless, their biological effects beyond RyR modulation and underlying mechanisms remain unexplored. This study employed Opicalcin1 (OpiCa1), the most bioactive calcin member, revealing that while it reduced cytosolic Ca²⁺ in H9c2 cardiomyocytes, it concurrently diminished cell viability and promoted apoptosis. Transcriptomics and Western blot analyses identified suppression of the negatively regulatory PI3K/Akt pathway as the mechanistic basis. In acute/chronic in vivo studies, high-dose OpiCa1 (≥50 mg/kg i.v.) exhibited minimal impact on body weight, histopathology, and organ indices, while a

SUBMITTER: Ma X 

PROVIDER: S-EPMC12656661 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature