Glucotoxicity results in apoptosis in H9c2 cells via alteration in redox homeostasis linked mitochondrial dynamics and polyol pathway and possible reversal with cinnamic acid.

Abstract

Several mechanisms have been proposed for the heart dysfunction during hyperglycemia. The aim of the present in vitro study is to elucidate the role of alterations in redox homeostasis in the induction of apoptosis during hyperglycemia in H9c2 cells via dysfunction in mitochondria and polyol pathway and evaluation of the beneficial effect of cinnamic acid against the same. The H9c2 cells were incubated with 33 mM glucose for 48 h to simulate the diabetic condition. Cell injury was confirmed with a significant increase of atrial natriuretic peptide and lactate dehydrogenase release. Alterations in the innate antioxidant system, polyol pathway, mitochondrial integrity, dynamics and apoptosis were investigated. Hyperglycemic insult has significantly affected redox homeostasis via depletion of superoxide dismutase, glutathione and enhanced reactive oxygen species generation. It also caused dysregulation in mitochondrial dynamics (fusion, fission proteins), dissipation of mitochondrial transmembrane potential and increased sorbitol accumulation. Finally, apoptosis was observed with upregulation of Bax, activation of caspase-3 and downregulation of Bcl-2. Cinnamic acid cotreatment increased the innate antioxidant status, improved mitochondrial function and prevented apoptosis in H9c2 cardiomyoblasts. Moreover, this in vitro model is found to be ideal for the elucidation of mechanisms at the cellular and molecular level of any physiological, pharmacological and toxicological incidents in H9c2 cells.

• Authors: Nair Anupama, M R Preetha Rani, G L Shyni, K G Raghu
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 53 Pg. 178-192 (Dec 2018) ISSN: 1879-3177 [Electronic] England
• PMID: 30144576 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Cinnamates
• Hypoglycemic Agents
• Polymers
• Reactive Oxygen Species
• polyol
• cinnamic acid
• Atrial Natriuretic Factor
• L-Lactate Dehydrogenase
• Glucose

Topics

• Animals
• Atrial Natriuretic Factor (metabolism)
• Cell Line
• Cell Survival (drug effects)
• Cinnamates (pharmacology)
• Glucose (pharmacology)
• Homeostasis (drug effects)
• Hyperglycemia (metabolism)
• Hypoglycemic Agents (pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondrial Dynamics (drug effects)
• Oxidation-Reduction
• Polymers (metabolism)
• Rats
• Reactive Oxygen Species (metabolism)