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Apoptosis induction by oxidized glycated LDL in human retinal capillary pericytes is independent of activation of MAPK signaling pathways
- Source :
- Molecular Vision
- Publication Year :
- 2009
- Publisher :
- Molecular Vision, 2009.
-
Abstract
- Background Pericyte loss is a cardinal feature of early diabetic retinopathy. We previously reported that highly oxidized-glycated low density lipoprotein (HOG-LDL) induces pericyte apoptosis in vitro. In this study, we investigated the role of the mitogen-activated protein kinase (MAPK) signaling pathways in HOG-LDL-induced apoptosis in human pericytes. Methods Human retinal capillary pericytes (HRCP) were exposed to native LDL (N-LDL) and HOG-LDL, and apoptosis was measured using flow cytometry. Time- and dose-dependent responses of extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) following exposure to N-LDL or HOG-LDL were determined using western blotting. U0126 (ERK inhibitor), SB203580 (p38 inhibitor), and SP600125 (JNK inhibitor) were used to determine the role of MAPK signaling in HOG-LDL-induced apoptosis. Results HOG-LDL induced apoptosis in HRCP in a dose-dependent manner at concentrations from 5 to 50 mg/l, with a constant effect from 50 to 200 mg/l. When compared to serum-free medium (SFM), this effect of HOG-LDL was found to be significant at all doses above 10 mg/l. In contrast, N-LDL at 200 mg/l did not induce apoptosis compared with SFM. Exposure to N-LDL versus HOG-LDL induced similar phosphorylation of ERK, p38, and JNK, peaking at 5 min, with similar dose-dependent responses up to 25 mg/l that were constant from 25 to 100 mg/l. Blocking of the ERK, p38, and JNK pathways did not inhibit pericyte apoptosis induced by HOG-LDL. Conclusions Our data suggest that apoptosis induced by HOG-LDL in HRCP is independent of the activation of MAPK signaling pathways.
- Subjects :
- Anthracenes
Glycation End Products, Advanced
Time Factors
MAP Kinase Signaling System
Pyridines
animal diseases
Imidazoles
JNK Mitogen-Activated Protein Kinases
Retinal Vessels
Apoptosis
respiratory system
p38 Mitogen-Activated Protein Kinases
Capillaries
Lipoproteins, LDL
Nitriles
otorhinolaryngologic diseases
Butadienes
Humans
lipids (amino acids, peptides, and proteins)
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Pericytes
Protein Kinase Inhibitors
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 10900535
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Molecular Vision
- Accession number :
- edsair.pmid..........e554c941e4ad8fc5e7b0e40a885d3033