PATHOPHYSIOLOGICAL ROLE OF INOSITOL 1, 4, 5-TRIPHOSPHATE RECEPTOR (IP3R) BINDING PROTEIN RELEASED WITH IP3 (IRBIT) IN THE MYOCARDIUM

DI MATTIA RA; GALLO D; CIARROCCHI S; GONANO LA; BLANCO PG; PORTIANSKY E; VALVERDE CA; CIANCIO MC; BLECKWEDEL F; ZELARAYAN LC; AIELLO EA; ORLOWSKI A

Congreso; Reunión Anual SAFIS 2023; 2023

IntroductionIP3 receptors (IP 3 Rs) are IP 3 gated Ca 2+ channels located on endoplasmic reticulum.IP 3 R binding protein released with IP 3 (IRBIT) was originally identified as a competitiveinhibitor of the receptor 1 . W hen IP 3 concentration rises in response to GPCR activationassociated with growth factors and neuroendocrine agonists , IRBIT is released fromIP 3 Rs 1 . IRBIT contains a serine rich N terminal domain with multiple phosphorylationsites that play a critical role allowing interaction and activation of several ion transportersand kinasesIRBIT is ubiquitous with important levels in brain tissuetestis, ovaries, lungs , kidneys ,and spleen 1 . IRBIT heart expression was described 1,2 , but its role in cardiac tissue hasnever been reported.Pathological cardiac hypertrophy (CH) is characterized by thickening of the leftventricular wall with cardiac dysfunction and implies a fibrotic response, apoptosis,deregulation of Ca +2 handling proteins, mitochondrial dysfunction, metabolic changes,and fetal gene reactivation. Cardiac hypertrophy has been associated with increasedPLC activity 3 and increased generation of IP 34 and overexpression of IP 3 Rs was found inboth human 5 and animal 6 models of heart failure. Since IP 3 R is involved in cardiachypertrophy, IRBIT might as well be associated with this pathology.