ABSTRAK PROPOSAL
ABSTRACT
THE ROLE OF QUERCETIN ON ENDOTHEL DISFUNCTION CAUSED BY HYPERLEPTIN : THE STUDY OF NUTRIPROTEOMIC AND NUTRIGENOMIC
M. Rasjad Indra, Satuman, Retty Ratnawati
Bacgrounds. The effect of obesity on vascular function is mediated by hormon leptin. Leptin has been proved to increase oxidative stress in endothelial cell. Quercetin is an isoflavone group which is commonly known as an active component in several plants. As a nutritional antioxidant, quercetin inhibits ICAM-1, VCAM-1 expression in endothelial cell by down regulate both phorbol 12-myrestate 13-acetate (PMA) and TNFa-induced ICAM-1 expression via inhibiting both activator protein-1 (AP-1) activation and c-Jun NH3-terminal kinase (JNK) pathway. Our preliminary research showed that the administration of 500 ng/ml leptin has decreased cellular proliferation and increased the monocyte chemoattractant protein-1 (MCP-1) in endothelial cells. There is no research has yet been carried out to elucidate the molecular mechanism of quercetin in preventing endothelial dysfunction caused by hyperleptin conditions. The aim of this research is to prove quercetin as an anti metabolic syndrome or anti-obesity bioactive agent. Methods. This research will be conducted for three years using an experimental design. In the first year, we use HUVECs which induced by high dose leptin followed by quercetin in four divided dose (0, 50, 125 and 625 uM). After incubated for six hours, leptin receptor, intracellular Ca2+ levels, and TNFa, MAPK and NF?B expression was examined as dependent variable. The second year research, by the same procedure as first years, will evaluate ET, ICAM-1 and VCAM-1 mRNA after treated with optimum dose of quercetin. The third year research will evaluate single nucleotide polymorphism of PPAR? and C/EBP? gene caused by leptin and quercetin in vivo. The expression of leptin receptor, TNFa, MAPK (ERK1/2), and p65 NF-?B will be detected using immunocytochemistry, Western blotting and ELISA, while intracellular Ca2++ levels will be identified using fluorescence staining. Hypothesis. The hypothesis of this research is that quercetin decrease the expression of leptin's receptor, the intracellular Ca2+ levels, and TNFa expression through the MAPK and NF?B inhibition in leptin-induced endothelial cell. Quercetin improves PPAR? and C/EBP gene polymorphism caused by hyperleptin in an obese rat models.
Key words: Leptin, obesity, quercetin, endothelial disfunction
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Shigenoi Haruki
THE ROLE OF QUERCETIN ON ENDOTHEL DISFUNCTION CAUSED BY HYPERLEPTIN : THE STUDY OF NUTRIPROTEOMIC AND NUTRIGENOMIC
M. Rasjad Indra, Satuman, Retty Ratnawati
Bacgrounds. The effect of obesity on vascular function is mediated by hormon leptin. Leptin has been proved to increase oxidative stress in endothelial cell. Quercetin is an isoflavone group which is commonly known as an active component in several plants. As a nutritional antioxidant, quercetin inhibits ICAM-1, VCAM-1 expression in endothelial cell by down regulate both phorbol 12-myrestate 13-acetate (PMA) and TNFa-induced ICAM-1 expression via inhibiting both activator protein-1 (AP-1) activation and c-Jun NH3-terminal kinase (JNK) pathway. Our preliminary research showed that the administration of 500 ng/ml leptin has decreased cellular proliferation and increased the monocyte chemoattractant protein-1 (MCP-1) in endothelial cells. There is no research has yet been carried out to elucidate the molecular mechanism of quercetin in preventing endothelial dysfunction caused by hyperleptin conditions. The aim of this research is to prove quercetin as an anti metabolic syndrome or anti-obesity bioactive agent. Methods. This research will be conducted for three years using an experimental design. In the first year, we use HUVECs which induced by high dose leptin followed by quercetin in four divided dose (0, 50, 125 and 625 uM). After incubated for six hours, leptin receptor, intracellular Ca2+ levels, and TNFa, MAPK and NF?B expression was examined as dependent variable. The second year research, by the same procedure as first years, will evaluate ET, ICAM-1 and VCAM-1 mRNA after treated with optimum dose of quercetin. The third year research will evaluate single nucleotide polymorphism of PPAR? and C/EBP? gene caused by leptin and quercetin in vivo. The expression of leptin receptor, TNFa, MAPK (ERK1/2), and p65 NF-?B will be detected using immunocytochemistry, Western blotting and ELISA, while intracellular Ca2++ levels will be identified using fluorescence staining. Hypothesis. The hypothesis of this research is that quercetin decrease the expression of leptin's receptor, the intracellular Ca2+ levels, and TNFa expression through the MAPK and NF?B inhibition in leptin-induced endothelial cell. Quercetin improves PPAR? and C/EBP gene polymorphism caused by hyperleptin in an obese rat models.
Key words: Leptin, obesity, quercetin, endothelial disfunction
--
Shigenoi Haruki
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