Effect of calcium channel blockers, nifedipine and benidipine, on death of cultured mouse mesangi al cells.
We examined the effects of the short-acting calcium channel blocker (CCB) nifedipine and the long-acting CCB benidipine on the death of mouse cultured mesangial cells induced by tumor necrosis factor alpha (TNF-alpha) and/or cycloheximide (CHX). Cell death was evaluated by a morphological study using semithin sections. The dead cells were divided into three types, i.e., apoptotic cells (type 1), necrotic cells (type 3) and other types of dead cells, the so-called 'secondary necrotic cells' or 'postapoptotic necrotic cells' (type 2). In the morphological study with semithin sections, cells in the presence of TNF-alpha or CHX and nifedipine or benidipine showed low percentages of all dead cell types with 24 h incubation. Both nifedipine and benidipine have protective effects against TNF-alpha or CHX. It is postulated that CCB might inhibit the apoptotic or necrotic processes by TNF-alpha or CHX with 24 h incubation. With 36 h incubation, CCB increased the percentages of all types of dead cells except for treatment with 1x10(-5) M benidipine and CHX. It appears that these cell-protective effects might be decreased after treatment with TNF-alpha or CHX and CCB for 36 h. In conclusion, the short-acting CCB nifedipine and the long-acting CCB benidipine have protective effects on mouse cultured mesangial cells against TNF-alpha or CHX. However, nifedipine and benidipine did not inhibit specific types of cell death using semithin sections in this study.
Shike
T
T
Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Tashiro
K
K
Gohda
T
T
Funabiki
K
K
Shirato
I
I
Tomino
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; C061004:benidipine; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase; D009543:Nifedipine