Methylglyoxal Induces Apoptosis Mediated by Reactive Oxygen Species in Bovine Retinal Pericytes.
10.3346/jkms.2004.19.1.95
- Author:
Jaetaek KIM
1
;
Jang Won SON
;
Jeong An LEE
;
Yeon Sahng OH
;
Soon Hyun SHINN
Author Information
1. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea. jtkim@cau.ac.kr
- Publication Type:Original Article
- Keywords:
Retina;
Pericytes;
Methylglyoxal;
Pyruvaldehyde;
Apoptosis;
Reactive Oxygen Species;
NF-kappaB
- MeSH:
Acetylcysteine/pharmacology;
Animals;
*Apoptosis;
Caspases/metabolism;
Cattle;
Cell Death;
Cell Survival;
DNA Fragmentation;
Dose-Response Relationship, Drug;
Enzyme-Linked Immunosorbent Assay;
Flow Cytometry;
Glucose/metabolism;
NF-kappa B/metabolism;
Nucleosomes/metabolism;
Oxidative Stress;
Pericytes/*drug effects;
Pyruvaldehyde/*pharmacology;
*Reactive Oxygen Species;
Retina/cytology/*drug effects
- From:Journal of Korean Medical Science
2004;19(1):95-100
- CountryRepublic of Korea
- Language:English
-
Abstract:
One of the histopathologic hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal (MGO), a reactive -dicarbonyl compound of glucose metabolism, on apoptotic cell death in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by ELISA showed that MGO (200 to 800 micrometer) induced apoptosis in a concentration-dependent manner. Intracellular reactive oxygen species were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF-kB activation and increased caspase- 3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF- kB inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO levels observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism and suggests that the nuclear activation of NF-kB are involved in the apoptotic process.
