Neuroprotective effect of propofol on necrosis and apoptosis following oxygen-glucose deprivation--relationship between mitochondrial membrane potential and mode of death.
Mitochondrial membrane potential (MMP) appears to play an important role in apoptotic cascade and has been proposed as an index for apoptosis or necrosis. We examined the neuroprotective effect of propofol on mode of death, focusing on MMP. Hippocampal cell culture was divided into three groups: control, oxygen-glucose deprivation for 30 min (30OGD), 90 min (90OGD). Propofol was added to each culture group at a concentration of 0 microM (Vehicle), 0.1 microM (Pro0.1) or 1.0 microM (Pro1.0). MMP was expressed as normalized JC-1 fluorescence. ATP content was assayed using the luciferin-luciferase reaction. Neuronal viability and appearance of apoptosis were also assessed. ATP content was decreased after OGD (0.276 +/- 0.115 microM/microg (control), 0.172 +/- 0.125 microM/microg (30OGD) and 0.096 +/- 0.092 microM/microg (90OGD)). Propofol did not alter ATP content. MMP was hyperpolarized after 30OGD (1.26 +/- 0.23 (vehicle), 1.29 +/- 0.13 (Pro0.1) and 1.18 +/- 0.06 (Pro1.0)) but was depolarized after 90OGD (0.77 +/- 0.04 (vehicle), 0.89 +/- 0.04 (Pro0.1), but Pro1.0 prevented depolarization (1.03 +/- 0.15 (P < 0.05)). Viability of cells significantly decreased to 50.3 +/- 5.7% (vehicle), 46.1 +/- 7.5% (Pro0.1), but Pro1.0 significantly salvaged neurons 65.1 +/- 6.2% (higher than vehicle and Pro0.1 value, P < 0.05) after 90OGD. At 24 h after OGD, TUNEL-positive cells were increased to 34.5 +/- 6.2% (vehicle), 26.7 +/- 7.9% (Pro0.1) and 30.4 +/- 7.1% (Pro1.0) in the 30OGD group. No pharmacological effect of propofol on the incidence of apoptosis was found. Propofol inhibited acute neuronal death accompanied with the maintenance of MMP but did not prevent subsequent apoptosis. Propofol induces a moratorium on neuronal death, during which pharmacological intervention might be able to prevent cell death.
Iijima
Takehiko
T
Department of Anesthesiology, Kyorin University, School of Medicine, Tokyo, Japan. iijmt@kyorin-u.ac.jp
Mishima
Tatsuya
T
Akagawa
Kimio
K
Iwao
Yasuhide
Y
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology; D000860:Hypoxia; D020287:In Situ Nick-End Labeling / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology*; D009336:Necrosis / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D015742:Propofol / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018696:Neuroprotective Agents; D005947:Glucose; D015742:Propofol