Mitochondrial complex I inhibition-augmented mitochondrial stress upon oxidative stress in Rotenone treated-RBA1

• Main Authors: Jia Nian Yu, 余佳年
• Other Authors: M. J. Jou
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/74124505473727454657

碩士 === 長庚大學 === 生物醫學研究所 === 98 === mitochondrial Complex I-augmented is the characteristics pathology of Parkinson’s disease. Rotenone was used for specifically complex I inhibitor for studied To quantitatively investigate how rotenone-enhanced defect alters mitochondrial reactive oxygen species (mROS) generation as well as mitochondrial Ca2+ -mediated oxidative stress, and mitochondrial fission and fusion machinery. The laser scanning multiple fluorescence imaging microscopy were performed. Our results demonstrate that the rotenone enhanced of mitochondrial complex I produced more reactive oxygen species (mROS) generation than rat brain astrocytes .Upon oxidative stress, the amount of complex I inhibition mROS generation and mitochondrial Ca2+-mediated malfunction were obligated to cause apoptotic events including subsequent opening of the mitochondrial permeability transition pore(MPTP) and phosphatidylserine (PS), cytochrome c /smac release. We transfection dominant negative drp1 in rotenone treated RBA1, our results revealed that fusion of mitochondrial reduced significantly mROS formation for less lipid peroxidation and ∆ψm loss. Whereas , fission of mitochondrial accelerated and fusion decreased ∆ψm depolarization, CL peroxidation , cCa2+, mCa2+ overload, and eventual cell death upon lethal doses of mitochondrial oxidative insults.Therefore, rearrangement of mitochondrial network via fission or fusion and mROS-mediated or cCa2+ , mCa2+-mediated in astrocytes may be play an critical role for neurodegenerative disease and contribute significantly for the future therapeutic prevention and treatment of complex I defects-associated neurodegeneration and aging.