Heterogeneous effects of distinct tocopherol analogues on NO release, cell volume, and cell death in microglial cells.
Tocopherols (vitamin E) are potent antioxidants as well as modulators of enzymes involved in signal transduction, like nitric oxide synthase (NOS). In primary murine microglial cells and in the microglial cell line BV-2, alpha-, gamma-, and delta-tocopherol and alpha-tocopherol acid succinate, respectively, promote nitric oxide (NO) release. The NOS inhibitors aminoguanidine and N(G)-methyl-L-arginine (L-NMMA) suppressed alpha- and gamma-tocopherol-induced NO release, but had no significant effect on delta-tocopherol- and alpha-tocopherol acid succinate-induced NO release. In BV-2 cells, but not in primary microglial cells, gamma- and delta-tocopherol and alpha-tocopherol acid succinate, respectively, led to cell death, characterized by exposition of phosphatidylserine on the cell surface, chromatin condensation, changes in cell volume, and formation of blebs on the cell surface. Aminoguanidine, L-NMMA, and the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) enhanced apoptosis in gamma-tocopherol-exposed cells and suppressed apoptosis in delta-tocopherol-treated cells, but had no effect on cells supplemented with alpha-tocopherol acid succinate. The NO donors sodium nitroprusside and 2-(N,N-diethylamino)-diazenolate 2-oxide enhanced apoptosis in gamma- or delta-tocopherol-treated cells, but rescued cells from alpha-tocopherol acid succinate-induced cell death.
Sacha
Beata
B
Division of Animal Physiology, Department of Cell Biology, University of Salzburg, Salzburg, Austria.
Zierler
Susanna
S
Lehnardt
Seija
S
Weber
Joerg R
JR
Kerschbaum
Hubert H
HH
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005911:Gliosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D024505:Tocopherols / Q000819:agonists* / Q000494:pharmacology / Q000627:therapeutic use; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use; D024504:gamma-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D024504:gamma-Tocopherol; D019001:Nitric Oxide Synthase; D024502:alpha-Tocopherol; C479072:delta-tocopherol; D024505:Tocopherols