Multiple analysis of mitochondrial metabolism, autophagy and cell death

Liu, D; Lai, Hong; Peyre, Félix; Brenner, Catherine

doi:10.1016/bs.mcb.2021.02.001

Cited by 2 publications

(1 citation statement)

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“…To conclude, conducted a robust high-throughput screening to search for cell death inhibitors. These assays are complementary to the previous low-throughput screens [28][29][30][31]. Our screening identified six inhibitors of cardiac cell death, which act through autophagy and metabolism reprogramming.…”

Section: Discussionmentioning

confidence: 85%

Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming

Liu

Peyre

Loissell-Baltazar

et al. 2022

Cells

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Improvement of anticancer treatments is associated with increased survival of cancer patients at risk of cardiac disease. Therefore, there is an urgent need for new therapeutic molecules capable of preventing acute and long-term cardiotoxicity. Here, using commercial and home-made chemolibraries, we performed a robust phenotypic high-throughput screening in rat cardiomyoblast cell line H9c2, searching for small molecules capable of inhibiting cell death. A screen of 1600 compounds identified six molecules effective in preventing necrosis and apoptosis induced by H2O2 and camptothecin in H9c2 cells and in rat neonatal ventricular myocytes. In cells treated with these molecules, we systematically evaluated the expression of BCL-2 family members, autophagy progression, mitochondrial network structure, regulation of mitochondrial fusion/fission, reactive oxygen species, and ATP production. We found that these compounds affect autophagy induction to prevent cardiac cell death and can be promising cardioprotective drugs during chemotherapy.

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Section: Discussionmentioning

confidence: 85%