Related Experiment Video

Updated: Oct 31, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

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RIPK3-Mediated Necroptosis in Diabetic Cardiomyopathy Requires CaMKII Activation

Yun Chen1,2, Xinshuai Li1, Yuyun Hua1

  • 1Department of Pharmacology, School of Pharmacy, Nantong University, Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, Nantong, 226001 Jiangsu, China.

Oxidative Medicine and Cellular Longevity
|July 1, 2021
PubMed

Insights

Diabetic cardiomyopathy involves CaMKII activation and necroptosis. RIPK3 deficiency and I1PP1 overexpression mitigate these effects, suggesting RIPK3-dependent therapeutic strategies for diabetic heart disease.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pathology

Background:

  • Ca2+/calmodulin-dependent protein kinase (CaMKII) activation is implicated in cardiovascular diseases.
  • Receptor-interaction protein kinase 3 (RIPK3)-mediated necroptosis contributes to cardiac dysfunction.
  • Diabetic cardiomyopathy (DCM) involves complex molecular pathways affecting heart function.

Purpose of the Study:

  • To investigate the roles and mechanisms of CaMKII activation and necroptosis in diabetic cardiomyopathy.
  • To explore the involvement of RIPK3 in these processes.
  • To assess the therapeutic potential of modulating these pathways.

Main Methods:

  • Utilized wild-type and RIPK3 knockout mice treated with streptozotocin to induce DCM.
  • Administered I1PP1 gene via recombinant adenovirus to assess its effects.
  • Evaluated cardiac function, myocardial injury, CaMKII activity, necroptosis markers (RIPK1, MLKL phosphorylation), and mitochondrial ultrastructure.

Main Results:

  • STZ-induced DCM mice exhibited aggravated cardiac dysfunction, CaMKII activation, and necroptosis.
  • RIPK3 deficiency ameliorated cardiac dysfunction, CaMKII activation, and necroptosis in DCM.
  • I1PP1 overexpression reversed DCM-related cardiac dysfunction and necroptosis in wild-type mice but not in RIPK3 knockout mice.

Conclusions:

  • CaMKII activation and necroptosis are augmented in DCM through a RIPK3-dependent pathway.
  • Targeting RIPK3-mediated necroptosis presents a potential therapeutic strategy for DCM.
  • Understanding this mechanism offers insights into novel treatments for diabetic heart disease.

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