Study of the roles of HSP27 in mitochondrial DNA mutation diseases

• Main Authors: Chin-Yi Chen, 陳靜怡
• Other Authors: Mingli Hsieh
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/96407197664163015786

碩士 === 東海大學 === 生命科學系 === 97 === Heat shock protein 27 has been reported to regulate the mitochondria-mediated cell apoptosis. From our previous study, reduced HSP27 was found in lymphoblastoid cells from myoclonus epilepsy with ragged-red fibers patients. Protein level of HSP27 was decreased in MERRF cybrid cells, especially evident in the phospho-HSP27. Overexpression of HSP27 in MERRF significantly decreases cell death under staurosporine treatment, indicating that HSP27 plays protective roles in cells harboring MERRF mtDNA mutation. From exogenous ATP addition to MERRF cybrid cells and the increased level of phospho-HSP27 in CPEO cybrid cells, we ruled out the possibility that lacking enough ATP results in a decreased phospho-HSP27. Furthermore, MERRF cells showed normal regulation of phospho-HSP27 and HSP27 under stress. To understand the mechanism of decreased HSP27 in MERRF cybrid cells, we examined the protein degration pathway of HSP27. Evidences from MG132, starvation and rapamycin treatments suggested that HSP27 may be degraded by the autophagic pathway. On the other hand, phospho-HSP27 may go through the proteasomal pathway. The increased basal levels of LC3 II and ATG12 were found in MERRF cybrid cells, indicating a constitutively activated autophagic pathway. It may explain, at least partially, why HSP27 was decreased in MERRF cybrid cells. This thesis provided understandings that HSP27 is degradated through the autophagic pathway and its’ protective role in MERRF cellular models. Regulation of HSP27 and the autophagic pathway might be therapeutic candidates for MERRF disease in the future.