caa a22 4500 463254716 CHVBK 20180405153351.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s10571-007-9220-7 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9220-7 Increased Caspase-2, Calpain Activations and Decreased Mitochondrial Complex II Activity in Cells Expressing Exogenous Huntingtin Exon 1 Containing CAG Repeat in the Pathogenic Range [Elektronische Daten] [Pritha Majumder, Swasti Raychaudhuri, Biswanath Chattopadhyay, Nitai Bhattacharyya] (1) Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of polymorphic CAG repeats beyond 36 at exon 1 of huntingtin gene (htt). To study cellular effects by expressing N-terminal domain of Huntingtin (Htt) in specific cell lines, we expressed exon 1 of htt that codes for 40 glutamines (40Q) and 16Q in Neuro2A and HeLa cells. (2) Aggregates and various apoptotic markers were detected at various time points after transfection. In addition, we checked the alterations of expressions of few apoptotic genes by RT-PCR. (3) Cells expressing exon 1 of htt coding 40Q at a stretch exhibited nuclear and cytoplasmic aggregates, increased caspase-1, caspase-2, caspase-8, caspase-9/6, and calpain activations, release of cytochrome c and AIF from mitochondria in a time-dependent manner. Truncation of Bid was increased, while the activity of mitochondrial complex II was decreased in such cells. These changes were significantly higher in cells expressing N-terminal Htt with 40Q than that obtained in cells expressing N-terminal Htt with 16Q. Expressions of caspase-1, caspase-2, caspase-3, caspase-7, and caspase-8 were increased while expression of Bcl-2 was decreased in cells expressing mutated Htt-exon 1. (4) Results presented in this communication showed that expression of mutated Htt-exon 1 could mimic the cellular phenotypes observed in Huntington's disease and this cell model can be used for screening the agents that would interfere with the apoptotic pathway and aggregate formation. Springer Science+Business Media, LLC, 2007 Poly Q aggregates nationallicence Huntington's disease nationallicence Apoptosis nationallicence Minocycline nationallicence Majumder Pritha Structural Genomics Section and Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, 700064, Kolkata, India aut Raychaudhuri Swasti Structural Genomics Section and Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, 700064, Kolkata, India aut Chattopadhyay Biswanath Structural Genomics Section and Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, 700064, Kolkata, India aut Bhattacharyya Nitai Structural Genomics Section and Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, 700064, Kolkata, India aut Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/8(2007-12-01), 1127-1145 0272-4340 27:8<1127 2007 27 10571 https://doi.org/10.1007/s10571-007-9220-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9220-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Majumder Pritha Structural Genomics Section and Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, 700064, Kolkata, India aut NATIONALLICENCE 700 1- Raychaudhuri Swasti Structural Genomics Section and Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, 700064, Kolkata, India aut NATIONALLICENCE 700 1- Chattopadhyay Biswanath Structural Genomics Section and Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, 700064, Kolkata, India aut NATIONALLICENCE 700 1- Bhattacharyya Nitai Structural Genomics Section and Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, 700064, Kolkata, India aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/8(2007-12-01), 1127-1145 0272-4340 27:8<1127 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer