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Updated: Sep 5, 2025

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
11:00

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Published on: September 18, 2017

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Ca2+/Calmodulin-Dependent Protein Kinase II Regulation by Inhibitor of Receptor Interacting Protein Kinase 3

Yuyun Hua1, Jianan Qian1, Ji Cao1

  • 1School of Pharmacy, Nantong University, Nantong 226001, China.

International Journal of Molecular Sciences
|July 9, 2022
PubMed

Insights

Advanced glycation end products (AGEs) induce cardiomyocyte necroptosis via RIPK3 and CaMKII signaling. Inhibiting Receptor interacting protein kinase 3 (RIPK3) protects against AGEs-induced cell damage and necroptosis.

Area of Science:

  • Cardiovascular Biology
  • Cellular Necrosis
  • Molecular Mechanisms

Background:

  • Necroptosis is a regulated form of necrosis crucial in cardiac injury.
  • Receptor interacting protein kinase 3 (RIPK3) is a key mediator of necroptosis.
  • The role of RIPK3 in advanced glycation end products (AGEs)-induced cardiomyocyte necroptosis remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of RIPK3 in AGEs-induced cardiomyocyte necroptosis.
  • To investigate the involvement of calcium/calmodulin-dependent protein kinase II (CaMKII) in this process.
  • To evaluate the protective effects of RIPK3 inhibition against AGEs-induced damage.

Main Methods:

  • Cardiomyocytes were stimulated with AGEs.
  • RIPK3 expression was modulated using siRNA and a specific inhibitor (GSK'872).
  • CaMKII activity, alternative splicing, oxidative stress, necroptosis, and cell damage were assessed.

Main Results:

  • AGEs increased RIPK3 expression, CaMKII activation, oxidative stress, and cardiomyocyte necroptosis and damage.
  • RIPK3 downregulation or inhibition corrected CaMKIIδ alternative splicing, reduced CaMKII activation, and attenuated oxidative stress.
  • RIPK3 inhibition protected cardiomyocytes against AGEs-induced necroptosis and cell damage.

Conclusions:

  • RIPK3 plays a critical role in AGEs-induced cardiomyocyte necroptosis.
  • AGEs-induced necroptosis involves CaMKII dysregulation and oxidative stress.
  • Targeting RIPK3 may offer a therapeutic strategy for AGEs-related cardiovascular complications.
Keywords:
advanced glycation end productscalcium/calmodulin-dependent protein kinase IIcardiomyocytesnecroptosisoxidative stressreceptor interacting protein kinase 3

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