1. Modulation of Mitochondrial Quality Control Processes by BGP-15 in Oxidative Stress Scenarios: From Cell Culture to Heart Failure
- Author
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Kalman Toth, Kitti Bruszt, Ferenc Gallyas, Laszlo Deres, Nikoletta Kálmán, Robert Halmosi, Balázs Radnai, Dominika Kovacs, Katalin Ordog, and Orsolya Horvath
- Subjects
Male ,0301 basic medicine ,Aging ,medicine.medical_treatment ,Cell Culture Techniques ,030204 cardiovascular system & hematology ,Mitochondrion ,medicine.disease_cause ,Mitochondrial Dynamics ,Rats, Inbred WKY ,Biochemistry ,Mitochondria, Heart ,0302 clinical medicine ,Piperidines ,Rats, Inbred SHR ,Natriuretic Peptide, Brain ,Oximes ,Myocytes, Cardiac ,Membrane Potential, Mitochondrial ,Organelle Biogenesis ,Chemistry ,General Medicine ,Cell biology ,mitochondrial fusion ,Hypertension ,Mitochondrial fission ,Research Article ,Dynamins ,Mitochondrial DNA ,Programmed cell death ,Article Subject ,Citrate (si)-Synthase ,DNA, Mitochondrial ,Electron Transport ,Mitochondrial Proteins ,03 medical and health sciences ,Oxygen Consumption ,medicine ,Animals ,Heart Failure ,QH573-671 ,Myocardium ,Insulin ,DNA ,Cell Biology ,medicine.disease ,Oxidative Stress ,030104 developmental biology ,Animals, Newborn ,Heart failure ,Genome, Mitochondrial ,Cytology ,Energy Metabolism ,Oxidative stress ,DNA Damage - Abstract
Heart failure (HF) is a complex chronic clinical disease characterized by among others the damage of the mitochondrial network. The disruption of the mitochondrial quality control and the imbalance in fusion-fission processes lead to a lack of energy supply and, finally, to cell death. BGP-15 (O-[3-piperidino-2-hydroxy-1-propyl]-nicotinic acid amidoxime dihydrochloride) is an insulin sensitizer molecule and has a cytoprotective effect in a wide variety of experimental models. In our recent work, we aimed to clarify the mitochondrial protective effects of BGP-15 in a hypertension-induced heart failure model and “in vitro.” Spontaneously hypertensive rats (SHRs) received BGP-15 or placebo for 18 weeks. BGP-15 treatment preserved the normal mitochondrial ultrastructure and enhanced the mitochondrial fusion. Neonatal rat cardiomyocytes (NRCMs) were stressed by hydrogen-peroxide. BGP-15 treatment inhibited the mitochondrial fission processes, promoted mitochondrial fusion, maintained the integrity of the mitochondrial genome, and moreover enhanced the de novo biogenesis of the mitochondria. As a result of these effects, BGP-15 treatment also supports the maintenance of mitochondrial function through the preservation of the mitochondrial structure during hydrogen peroxide-induced oxidative stress as well as in an “in vivo” heart failure model. It offers the possibility, which pharmacological modulation of mitochondrial quality control under oxidative stress could be a novel therapeutic approach in heart failure.
- Published
- 2021
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