TY - JOUR
T1 - Region-specific attenuation of a trypsin-like protease in substantia nigra following dopaminergic neurotoxicity by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
AU - Usha, Rajamma
AU - Muralikrishnan, Dhanasekharan
AU - Thomas, Bobby
AU - Ghosh, Sagarmoy
AU - Mandal, Chhabinath
AU - Mohanakumar, Kochupurackal P.
N1 - Funding Information:
Financed by CSIR and DST. UR is a Senior Research Associate (Scientists’ Pool) of CSIR, Government of India. BT, DM and SG are recipients of CSIR Senior Research Fellowships.
PY - 2000/11/3
Y1 - 2000/11/3
N2 - We analysed apoptosis, caspase-1 and -3, and trypsin-like protease activity in the nigrostriatal pathway during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. MPTP injected (30 mg/kg, i.p., twice, 16 h apart) mice were sacrificed on 1, 2 and 7 days. DNA extracted from nucleus caudatus putamen (NCP) and substantia nigra (SN) was subjected to agarose gel electrophoresis. Typical apoptotic-like DNA cleavage was absent in SN or NCP after this dose of MPTP. A trypsin-like protease activity was significantly decreased in SN and not in NCP. While caspase-3 activity in the whole brain was increased significantly, caspase-1 activity was unaffected. Striatal dopamine content was decreased to 75% by 7 days. The absence of typical DNA 'ladder' when there was severe striatal dopamine depletion suggests that in vivo MPTP-mediated dopaminergic neurotoxicity may not involve apoptotic cell death, and explains why in mice MPTP-induced dopamine depletion is transient. The region-specific decrease in trypsin-like protease activity and absence of caspase-3 activation in SN signify the importance of trypsin-like protease in the regulation of apoptosis in MPTP-neurotoxicity in mice. (C) 2000 Elsevier Science B.V.
AB - We analysed apoptosis, caspase-1 and -3, and trypsin-like protease activity in the nigrostriatal pathway during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. MPTP injected (30 mg/kg, i.p., twice, 16 h apart) mice were sacrificed on 1, 2 and 7 days. DNA extracted from nucleus caudatus putamen (NCP) and substantia nigra (SN) was subjected to agarose gel electrophoresis. Typical apoptotic-like DNA cleavage was absent in SN or NCP after this dose of MPTP. A trypsin-like protease activity was significantly decreased in SN and not in NCP. While caspase-3 activity in the whole brain was increased significantly, caspase-1 activity was unaffected. Striatal dopamine content was decreased to 75% by 7 days. The absence of typical DNA 'ladder' when there was severe striatal dopamine depletion suggests that in vivo MPTP-mediated dopaminergic neurotoxicity may not involve apoptotic cell death, and explains why in mice MPTP-induced dopamine depletion is transient. The region-specific decrease in trypsin-like protease activity and absence of caspase-3 activation in SN signify the importance of trypsin-like protease in the regulation of apoptosis in MPTP-neurotoxicity in mice. (C) 2000 Elsevier Science B.V.
KW - Apoptosis
KW - Caspase-1
KW - Caspase-3
KW - Dopamine depletion
KW - Experimental parkinsonism
KW - Striatum
KW - Trypsin inhibition
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U2 - 10.1016/S0006-8993(00)02802-X
DO - 10.1016/S0006-8993(00)02802-X
M3 - Article
C2 - 11056198
AN - SCOPUS:0034602134
SN - 0006-8993
VL - 882
SP - 191
EP - 195
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -