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Methylglyoxal induces apoptosis mediated by reactive oxygen species in bovine retinal pericytes.

Kim J, Son JW, Lee JA, Oh YS, Shinn SH - J. Korean Med. Sci. (2004)

Bottom Line: NF-kappaB activation and increased caspase-3 activity were detected.Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB 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-kappaB are involved in the apoptotic process.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea. jtkim@cau.ac.kr

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 alpha-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 microM) 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-kappaB activation and increased caspase-3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB 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-kappaB are involved in the apoptotic process.

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Dose-dependent cytotoxic effects of MGO in retinal pericytes. Cytotoxicity was measured by MTT assay after 6 hr. Data are means±SD of triplicate experiments. *p<0.05, **p<0.01.
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Figure 1: Dose-dependent cytotoxic effects of MGO in retinal pericytes. Cytotoxicity was measured by MTT assay after 6 hr. Data are means±SD of triplicate experiments. *p<0.05, **p<0.01.

Mentions: MGO produced a progressive cytotoxic effect on retinal pericytes with increasing concentration, reaching maximum cytotoxicity with 40% damaged cells at 800 M after 6 hr incubation (Fig. 1). A statistically significant cytotoxicity occurred at a concentration of 200 µM (p<0.05) or greater (p<0.01).


Methylglyoxal induces apoptosis mediated by reactive oxygen species in bovine retinal pericytes.

Kim J, Son JW, Lee JA, Oh YS, Shinn SH - J. Korean Med. Sci. (2004)

Dose-dependent cytotoxic effects of MGO in retinal pericytes. Cytotoxicity was measured by MTT assay after 6 hr. Data are means±SD of triplicate experiments. *p<0.05, **p<0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822272&req=5

Figure 1: Dose-dependent cytotoxic effects of MGO in retinal pericytes. Cytotoxicity was measured by MTT assay after 6 hr. Data are means±SD of triplicate experiments. *p<0.05, **p<0.01.
Mentions: MGO produced a progressive cytotoxic effect on retinal pericytes with increasing concentration, reaching maximum cytotoxicity with 40% damaged cells at 800 M after 6 hr incubation (Fig. 1). A statistically significant cytotoxicity occurred at a concentration of 200 µM (p<0.05) or greater (p<0.01).

Bottom Line: NF-kappaB activation and increased caspase-3 activity were detected.Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB 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-kappaB are involved in the apoptotic process.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea. jtkim@cau.ac.kr

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 alpha-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 microM) 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-kappaB activation and increased caspase-3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB 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-kappaB are involved in the apoptotic process.

Show MeSH
Related in: MedlinePlus