title: Involvement of oxidative stress in bee venom-induced inhibition of Na+/glucose cotransporter in renal proximal tubule cells.
abstract: 1. The present study was conducted to examine the involvement of oxidative stress in bee venom-induced inhibition of the Na+/glucose cotransporter (alpha-methyl-d-glucopyranoside (alpha-MG) uptake), a typical functional marker of proximal tubules, in primary cultured rabbit renal proximal tubule cells (PTC). 2. Bee venom (> or = 1 microg/mL) increased lipid peroxide (LPO) formation over 30 min. The increase in [(3)H]-arachidonic acid (AA) release and LPO formation and the inhibition of alpha-MG uptake induced by bee venom (1 microg/mL) and melittin (a major component of bee venom; 0.5 microg/mL) were blocked by N-acetyl-l-cysteine, vitamin C and vitamin E, anti-oxidants. 3. Bee venom- and melittin-induced increases in LPO formation and inhibition of alpha-MG uptake were significantly prevented by mepacrine and AACOCF(3), phospholipase A(2) inhibitors. In addition, nordihydroguaiareic acid (a lipoxygenase inhibitor) and econazole (a cytochrome P-450 epoxygenase inhibitor), but not indomethacin (a cyclo-oxygenase inhibitor), prevented bee venom- and melittin-induced increases in LPO formation and inhibition of alpha-MG uptake. 4. Nordihydroguaiareic acid prevented bee venom- and melittin-induced increases in Ca(2+) uptake. Moreover, anti- oxidants significantly prevented bee venom- and melittin-induced increases in Ca(2+) uptake. 5. In conclusion, bee venom inhibits alpha-MG uptake via the phospholipase A(2)-oxidative stress-Ca(2+) signalling cascade in primary cultured rabbit renal proximal tubule cells.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju, Korea. hjhan@chonnam.ac.kr
authors.forename: Ho Jan
authors.initials: HJ
authors.lastname: Han
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Jang Hern
authors.initials: JH
authors.lastname: Lee
authors.forename: Byeong Cheol
authors.initials: BC
authors.lastname: Yoon
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
authors.forename: Woong Chon
authors.initials: WC
authors.lastname: Mar
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung Keel
authors.initials: SK
authors.lastname: Kang
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D001514:Bee Venoms / Q000494:pharmacology*; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects*; D010741:Phospholipases A / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D001514:Bee Venoms; D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D009004:Monosaccharide Transport Proteins; C081565:arachidonyltrifluoromethane; D016718:Arachidonic Acid; D010741:Phospholipases A; D011796:Quinacrine; D002118:Calcium