Faculty Collaboration Database

Glucotoxicity results in apoptosis in H9c2 cells via alteration in redox homeostasis linked mitochondrial dynamics and polyol pathway and possible reversal with cinnamic acid. Toxicol In Vitro 2018 Dec;53:178-192

Date

08/26/2018

Pubmed ID

30144576

DOI

10.1016/j.tiv.2018.08.010

Scopus ID

2-s2.0-85052621776 (requires institutional sign-in at Scopus site)   20 Citations

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.

Author List

Anupama N, Preetha Rani MR, Shyni GL, Raghu KG

Author

Anupama Nair Postdoctoral Researcher 3 in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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