title: Differential regulation of caspase-2 in MPP⁺-induced apoptosis in primary cortical neurons.
abstract: Parkinson's disease (PD), among the most common neurodegenerative diseases worldwide for which there is no cure, is characterized as progressive dopaminergic neuron loss in the substantia nigra through an unknown mechanism. Administering 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) causes neuronal cell death and Parkinsonism in humans. Commonly used in animal models of PD, MPTP can metabolize to 1-methyl-4-phenylpyridinium (MPP(+)); however, the detailed mechanism through which MPP(+) causes neuronal cell death remains undetermined. Previous reports have indicated those knockout mice with Bcl-2 associated protein X (Bax) or caspase-2, two mitochondrial outer membrane permeabilization inducers, are resistant to MPTP administration, suggesting that mitochondria are involved in MPP(+)-triggered apoptosis. Our previous study showed that MPP(+)-triggered apoptosis can be distinguished from spontaneous apoptosis of primary cortical neurons. In the present study, we verified the involvement of mitochondria in MPP(+)-induced and spontaneous apoptosis in cortical neurons through confocal microscope analysis. We demonstrated that caspase-2 activation is specific to MPP(+)-induced apoptosis and occurs before Bax translocation to the mitochondria. Caspase-2 activation is one of the few early molecular events identified in PD models.
authors: Department of Molecular Biology and Human Genetics, Tzu-Chi University, No. 701, Section 3, Zhong-Yang Road, 97004 Hualien, Taiwan, ROC.
authors: Hsin-I
authors: HI
authors: Hu
authors: Department of Molecular Biology and Human Genetics, Tzu-Chi University, No. 701, Section 3, Zhong-Yang Road, 97004 Hualien, Taiwan, ROC; Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan, ROC.
authors: Hsin-Hou
authors: HH
authors: Chang
authors: Department of Molecular Biology and Human Genetics, Tzu-Chi University, No. 701, Section 3, Zhong-Yang Road, 97004 Hualien, Taiwan, ROC; Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan, ROC. Electronic address: dssun@mail.tcu.edu.tw.
authors: Der-Shan
authors: DS
authors: Sun
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053143:Caspase 2 / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000201:enzymology / Q000473:pathology; D061251:Primary Cell Culture; D021381:Protein Transport
chemical_list: C090208:Casp2 protein, mouse; D053143:Caspase 2; D015655:1-Methyl-4-phenylpyridinium
keywords: Apoptosis; Caspase-2; MPP(+); Mitochondria; Parkinson׳s disease; Primary cortical neurons