期刊
BIOCHEMICAL JOURNAL
卷 446, 期 -, 页码 359-371出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20111495
关键词
apoptosis; cytoskeleton-associated proteins; Huntington's disease; induced pluripotent stem cell (iPSC); oxidative stress; proteomic analysis
资金
- Next-Generation BioGreen 21 Program [PJ008116062011]
- Rural Development Administration, Republic of Korea
- Korea Food and Drug Administration [S-11-04-2-SJV-993-0-H]
- Korea Health Technology R&D Project of the Ministry of Health and Welfare of the Republic of Korea [A111016]
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2012R1A1A2006827, 2010-0021532, 2011-0026986]
- Chonbuk National University
- Korea Health Promotion Institute [A111016] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2010-0021532, 2012R1A1A2006827] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
HD (Huntington's disease) is a devastating neurodegenerative genetic disorder caused by abnormal expansion of CAG repeats in the HTT (huntingtin) gene. We have recently established two iPSC (induced pluripotent stem cell) lines derived from a HD patient carrying 72 CAG repeats (HD-iPSC). In order to understand the proteomic profiles of HD-iPSCs, we have performed comparative proteomic analysis among normal hESCs (human embryonic stem cells; H9), iPSCs (551-8) and HD-iPSCs at undifferentiated stages, and identified 26 up- and down-regulated proteins. Interestingly, these differentially expressed proteins are known to be involved in different biological processes, such as oxidative stress, programmed cell death and cellular oxygen-associated proteins. Among them, we found that oxidative stress-related proteins, such as SOD1 (superoxide dismutase 1) and Prx (peroxiredoxin) families are particularly affected in HD-iPSCs, implying that HD-iPSCs are highly susceptible to oxidative stress. We also found that BTF3 (basic transcription factor 3) is up-regulated in HD-iPSCs, which leads to the induction of ATM (ataxia telangiectasia mutated), followed by activation of the p53-mediated apoptotic pathway. In addition, we observed that the expression of cytoskeleton-associated proteins was significantly reduced in HD-iPSCs, implying that neuronal differentiation was also affected. Taken together, these results demonstrate that HD-iPSCs can provide a unique cellular disease model system to understand the pathogenesis and neurodegeneration mechanisms in HD, and the identified proteins from the present study may serve as potential targets for developing future HD therapeutics.
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