Involvement of oxidative stress in bee venom-induced inhibition of Na+/glucose cotransporter in renal proximal tubule cells.
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.
Han
Ho Jan
HJ
Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju, Korea. hjhan@chonnam.ac.kr
Park
Soo Hyun
SH
Lee
Jang Hern
JH
Yoon
Byeong Cheol
BC
Park
Kwon Moo
KM
Mar
Woong Chon
WC
Lee
Hye Jung
HJ
Kang
Sung Keel
SK
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
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