title: Involvement of NF-kappaB in high glucose-induced alteration of alpha-methyl-D-glucopyranoside (alpha-MG) uptake in renal proximal tubule cells.
abstract: Although recent data have shown that nuclear factor-kappa B (NF-kappaB) is activated in tubules and glomeruli in various experimental models of renal injury, biological significance of NF-kappaB activation in diabetic renal injury is not clear. Thus, this study performed to investigate involvement of NF-kappaB in high glucose-induced Na+/glucose cotransporters' dysfunction in primary cultured renal proximal tubules cells (PTCs). Treatment with 25 mM glucose for 48 hr increased NF-kappaB DNA binding activity by five times compared to 5 mM glucose (control). The specificity of the binding reaction was confirmed by competition studies. The level of NF-kappaB p65 protein by treatment with 25 mM glucose for 48 hr was increased by about 2-fold compared to 5 mM glucose in the nuclear extracts. Also, Western blot analysis of IkappaB-alpha protein showed that levels of IkappaB-alpha protein were clearly decreased after incubation with 25 mM glucose compare to 5 mM glucose. To examine the relationship of NF-kappaB and oxidative stress or PKC in the high glucose-induced inhibition of [14C]- alpha-methyl-D-glucopyranoside (alpha-MG) uptake, PKC inhibitors and antioxidants effectively blocked high glucose-induced activation of NF-kappaB although these themselves had no significant effects. In addition, high glucose-induced inhibition of alpha-MG uptake was prevented by NF-kappaB inhibitors. In conclusion, high glucose inhibits, in part, alpha-MG uptake through NF-kappaB activation mediated by oxidative stress and PKC activation in the primary cultured rabbit renal proximal tubule cells.
authors: Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University. Hjhan@chonnam.ac.k
authors: Ho Jae
authors: HJ
authors: Han
authors: Young Jin
authors: YJ
authors: Jeon
authors: Yun Jung
authors: YJ
authors: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008757:Methylglucosides / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D013379:Substrate Specificity; D051996:Transcription Factor RelA
chemical_list: D000975:Antioxidants; D020672:I-kappa B Proteins; D008054:Lipid Peroxides; D008757:Methylglucosides; D016328:NF-kappa B; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D012964:Sodium; D011493:Protein Kinase C; D005947:Glucose