Details

Autor(en) / Beteiligte

• Yang, Lichuan
• Matthews, Russell T
• Schulz, Jorg B
• Klockgether, Thomas
• Liao, Andrew W
• Martinou, Jean-Claude
• Penney, John B., Jr
• Hyman, Bradley T
• Beal, M. Flint

Titel

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyride Neurotoxicity Is Attenuated in Mice Overexpressing Bcl-2

Ist Teil von

• The Journal of neuroscience, 1998-10, Vol.18 (20), p.8145-8152

Ort / Verlag

United States: Soc Neuroscience

Erscheinungsjahr

1998

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The proto-oncogene Bcl-2 rescues cells from a wide variety of insults. Recent evidence suggests that Bcl-2 protects against free radicals and that it increases mitochondrial calcium-buffering capacity. The neurotoxicity of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyride (MPTP) is thought to involve both mitochondrial dysfunction and free radical generation. We therefore investigated MPTP neurotoxicity in both Bcl-2 overexpressing mice and littermate controls. MPTP-induced depletion of dopamine and loss of [3H]mazindol binding were significantly attenuated in Bcl-2 overexpressing mice. Protection was more profound with an acute dosing regimen than with daily MPTP administration over 5 d. 1-Methyl-4-phenylpyridinium (MPP+) levels after MPTP administration were similar in Bcl-2 overexpressing mice and littermates. Bcl-2 blocked MPP+-induced activation of caspases. MPTP-induced increases in free 3-nitrotyrosine levels were blocked in Bcl-2 overexpressing mice. These results indicate that Bcl-2 overexpression protects against MPTP neurotoxicity by mechanisms that may involve both antioxidant activity and inhibition of apoptotic pathways.