Programmed Cell Death in the Left and Right Ventricle of the Late Phase of Post-Infarction Heart Failure
Open Access
- 20 October 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (20), 7782
- https://doi.org/10.3390/ijms21207782
Abstract
While necroptosis has been shown to contribute to the pathogenesis of post-infarction heart failure (HF), the role of autophagy remains unclear. Likewise, linkage between these two cell death modalities has not been sufficiently investigated. HF was induced by 60-min left coronary occlusion in adult Wistar rats and heart function was assessed 6 weeks later followed by immunoblotting analysis of necroptotic and autophagic proteins in both the left (LV) and right ventricle (RV). HF had no effect on RIP1 and RIP3 expression. PhosphoSer229-RIP3, acting as a pro-necroptotic signal, was increased in LV while deceased in RV of failing hearts. Total MLKL was elevated in RV only. Decrease in pSer555-ULK1, increase in pSer473-Akt and no significant elevation in beclin-1 and LC3-II/I ratio indicated rather a lowered rate of autophagy in LV. No beclin-1 upregulation and decreased LC3 processing also suggested the inhibition of both autophagosome formation and maturation in RV of failing hearts. In contrast, p89 PARP1 fragment, a marker of executed apoptosis, was increased in RV only. This is the first study showing a different signaling in ventricles of the late phase of post-infarction HF, highlighting necroptosis itself rather than its linkage with autophagy in LV, and apoptosis in RV.Funding Information
- APVV (APVV-15-607)
- Czech Health Research Council (grant No. 15-27735A)
This publication has 63 references indexed in Scilit:
- TNF can activate RIPK3 and cause programmed necrosis in the absence of RIPK1Cell Death & Disease, 2013
- Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 KinaseCell, 2012
- AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1Nature, 2011
- Autophagy: cellular and molecular mechanismsThe Journal of Pathology, 2010
- Phosphorylation-Driven Assembly of the RIP1-RIP3 Complex Regulates Programmed Necrosis and Virus-Induced InflammationCell, 2009
- Akt-dependent and -independent mechanisms of mTOR regulation in cancerCellular Signalling, 2009
- The role of autophagy in the heartCell Death & Differentiation, 2008
- An Atg4B Mutant Hampers the Lipidation of LC3 Paralogues and Causes Defects in Autophagosome ClosureMolecular Biology of the Cell, 2008
- FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cellsThe Journal of cell biology, 2008
- Cardiac autophagy is a maladaptive response to hemodynamic stressJCI Insight, 2007