Advanced glycation end products-induced apoptosis attenuated by PPARdelta activation and epigallocatechin gallate through NF-kappaB pathway in human embryonic kidney cells and human mesangial cells.
BACKGROUND
Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor delta (PPARdelta) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs).


METHODS
The HEK cells and HMC were separated into the following groups: 100 microg/mL AGE alone for 18 h; AGE treated with 1 microM L-165041 or 10 microM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-kappaB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined.


RESULTS
AGE significantly increased tumour necrosis factor-alpha (TNF-alpha), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pre-treatment with L-165041 or EGCG. AGE-induced nuclear factor-kappaB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC.


CONCLUSIONS
This study demonstrated that PPARdelta agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARdelta agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy.
Liang
Yao-Jen
YJ
Department and Institute of Life Science, Fu-Jen Catholic University, Taipei, Taiwan.
Jian
Jhin-Hao
JH
Liu
Yuan-Chun
YC
Juang
Shiow-Jen
SJ
Shyu
Kou-Gi
KG
Lai
Ling-Ping
LP
Wang
Bao-Wei
BW
Leu
Jyh-Gang
JG
D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D050527:Mesangial Cells / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D047494:PPAR delta / Q000378:metabolism*; D010642:Phenoxyacetates; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D016328:NF-kappa B; D047494:PPAR delta; D010642:Phenoxyacetates; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate