Transplantation of Pep-1-labeled Mitochondria Protection Against a 6-OHDA-induced Neurotoxicity in Rats

Jui-Chih Chang ； Ko-Hung Liu ； Chieh-Sen Chuang ； Shey-lin Wu ； Shou-Jen Kuo ； Chin-San Liu

《The Changhua Journal of Medicine》 11卷1期 (2013/09) Pp. 8-17

並列摘要

Parkinson's disease (PD) is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This consequence cause cellular damage and death mediated by oxidative stress and excitotoxicity. The present study further examined to feasibility of the neuroprotective effect through penetrating of mitochondria conjugated Pep-1 (Pep-1-Mito) in the 6-OHDA-lesioned rat model of PD in vivo. Methods and The different dosage of Pep-1-Mito (0.525, 1.05 and 2.1μg) was injected into the medial forebrain bundle (MFB) of 21 days 6-OHDA-lesioning Parkison's rats, a same position of unilateral toxin conduction. The motor function was evaluated by rotational response to apomorphine at every 2 weeks after injection Pep-1-Mito or infusion of vehicle (Sham group). The matrix protein of donor mitochondria from 143B osteosacroma control cybrid (C2) was tagged with the green fluorescent protein (GFP) for trace. After 12 weeks transplantation of Pep-1-Mito, GFP signal derived from donor mitochondria was not observed in the area of substantia nigra (SN) and striatum (ST). However, motor function of PD rat was significant improved by injection groups of 1.05 and 0.525μg Pep-1-Mito in contrary to 2.1μg group, comparing to sham group. Meanwhile, the highest performance of tyrosine hydroxylase (TH) and survival of dopaminergic neuron in SN, as well as mitochondrial complex (CI, III and V) activities and copy number of mitochondrial DNA, were also found in the group of 1.05μg relative to other dose groups. Moreover, the dominant upregulation of OPA1, MFN2 and Drp1 in contrast to Fis1, accompanying mitophagy induction showed by uprequlation of Parkin, PINK1, LC3, polyubiquitin was also found in rats with 1.05μg Pep-1-Mito. It implied that via benefit of Pep-1-Mito could resulted from intervention of mitochondrial turnover.

並列關鍵字

Parkinson's disease ； Pep-1 ； Mitochondrial delivery ； Mitochondrial functions ； Mitochondrial turnover