Modulation of mitochondrial function by stem cell-derived cellular components

• Published in: Biochemical and biophysical research communications 2014-06, Vol.448 (4), p.403-408
• Main Authors: Liu, Tian, Im, Wooseok, Lee, Soon-Tae, Ban, Jae-Jun, Chai, Ye Jin, Lee, Mijung, Mook-Jung, Inhee, Chu, Kon, Kim, Manho
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Adult Stem Cells - metabolism; Animals; Apoptosis; Apoptosis - physiology; Cell Extracts - pharmacology; Cell Line; Human adipose stem cells; Humans; Huntingtin Protein; Huntington Disease - metabolism; Huntington Disease - pathology; Huntington Disease - therapy; Membrane Potential, Mitochondrial; Mice; Mitochondria; Mitochondria - metabolism; Multipotent Stem Cells - metabolism; Mutant huntingtin; Mutant Proteins - genetics; Mutant Proteins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural Stem Cells - metabolism; Neural Stem Cells - pathology; Neurons - metabolism; Neurons - pathology; Oxidative Stress; p53; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.04.129

•hASC extracts prevent mHtt-induced apoptosis.•hASC extracts prevent mHtt-induced mitochondrial dysfunction.•hASC extracts down-regulate endogenous p53 in vivo and in vitro.•hASC extracts destabilize p53 and disrupt interaction of mHtt and p53. Huntington’s disease (HD) is the most common hereditary neurodegenerative diseases, in which the loss of striatal neuron caused by the aggregation of mutant huntingtin protein (mHtt) is the main pathological feature. Our previous studies have demonstrated that human adipose stem cells (hASC) and its extracts can slow down the progression of HD in vitro and in vivo. hASC are readily accessible adult stem cells, and the cytosolic extracts contain a number of neurotrophic factors. Here, we further explored the role of the hASC extracts in neuronal death and mitochondrial function in HD. Our results showed that the hASC extracts prevent mHtt-induced cell toxicity and cell apoptosis. Moreover, the hASC extracts recovered mHtt-induced mitochondrial oxidative stress and reduced mitochondrial membrane potential. The hASC extracts blocked the interaction between p53 and mHtt, and decreased the endogenous p53 levels at both transcriptional and post-translational levels, resulting in the instability of p53 and increased neuronal survival. Taken together, these findings implicate protective roles of hASC extracts in mHtt-induced mitochondrial apoptosis, providing insights into the molecular mechanism of the hASC in the therapeutic strategy of HD.