• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1993-1998
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• 2016

The effects of carbon-ion irradiation on cancer cell telomere function have not been comprehensively studied. In our previous report cancer cells with telomere dysfunction were more sensitive to carbon-ion irradiation, but the underlying mechanisms remained unclear. Here we found that telomerase activity was suppressed by carbon-ion irradiation via hTERT down-regulation. Inhibition of telomere activity by MST-312 further increased cancer cell radiosensitivity to carbon-ion radiation. hTERT suppression caused by either carbon-ion irradiation or MST-312 impaired mitochondrial function, as indicated by decreased membrane potential, mtDNA copy number, mitochondrial mass, total ATP levels and elevated reactive oxygen species (ROS). PGC-$1{\alpha}$ expression was repressed after carbion-ion irradiation, and hTERT inhibition by MST-312 could further exacerbate this effect. Lowering the mitochondrial ROS level by MitoTEMPO could partially counteract the induction of cellular senescence induced by carbon-ion radiation and MST-312 incubation. Taken together, the current data suggest that telomere-mitochondrion links play a role in the induction of senescence in MCF-7 cells after carbon-ion irradiation.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.744-754
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• 2020

We investigated the whether endurance exercise and MitoQ intake mediated neuroprotection are associated with mitochondrial function in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP) -induced mice model of Parkinson's disease. C57BL/6 male mice were randomly assigned to five groups: Normal Conrol(NC, n=10), MPTP Control(MC, n=10), MPTP +MitoQ(MQ, n=10), MPTP + Exercise(ME, n=10) and MPTP + MitoQ + Exercise(MQE, n=10). Exercise intervention groups performed the treadmill exercise for 5days/week for 5 weeks with gradual increase of intensity. MitoQ intake groups consumed the MitoQ at a concentration of 250μmol by dissolving with water during experiment period. Our data demonstrated that ME and MQE group restored MPTP-induced motor dysfunction. In addition, treatment groups(MQ, ME and MQE) increased tyrosine hydroxylase levels, and suppressed the accumulation of α-synuclein levels. Futhermore, treatment groups modulated the mitochondrial function such as upregulated mitochondrial biogenesis, increased antioxidant enzyme, enhanced a anti-apoptotic protein(e.g., BCL2), and reduced a pro-apoptotic protein(e.g., BAX). Taken together, these results suggested that endurance exercise and MitoQ intake-mediated increase in mitochondrial function contributes to improvement of aggravated dopaminergic neuronal, resulting in attenuation of motor function of Parkinson's disease.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.283-289
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• 2015

This study surveys the improvement characteristics in old-aged muscular mitochondria by bio-active materials coated fabric (BMCF). To observe the effects, the fabric (10 and 30%) was worn to old-aged rat then the oxygen consumption efficiency and copy numbers of mitochondria, and mRNA expression of apoptosis- and mitophagy-related genes were verified. By wearing the BMCF, the oxidative respiration significantly increased when using the 30% materials coated fabric. The mitochondrial DNA copy number significantly decreased and subsequently recovered in a dose-dependent manner. The respiratory control ratio to mitochondrial DNA copy number showed a dose-dependent increment. As times passed, Bax, caspase 9, PGC-$1{\alpha}$ and ${\beta}$-actin increased, and Bcl-2 decreased in a dose-dependent manner. However, the BMCF can be seen to have had no effect on Fas receptor. PINK1 expression did not change considerably and was inclined to decrease in control group, but the expression was down-regulated then subsequently increased with the use of the BMCF in a dose-dependent manner. Caspase 3 increased and subsequently decreased in a dose-dependent manner. These results suggest that the BMCF invigorates mitophagy and improves mitochondrial oxidative respiration in skeletal muscle, and in early stage of apoptosis induced by the BMCF is not related to extrinsic death-receptor mediated but mitochondria-mediated signaling pathway.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.5.1-5.14
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• 2018

Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stress-induced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol ($10{\mu}M$) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPK-PGC-$1{\alpha}$ signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.

• Journal of Life Science
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• v.28 no.12
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• pp.1455-1460
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• 2018

Due to a rapidly expanding aging population, the incidence of degenerative bone disease has increased, and efforts to handle the issue using regenerative medicine have become more important. In order to control various bone diseases such as osteoarthritis and osteoporosis, regenerative medicine utilizing adult stem cells has been extensively studied. And it is now clear that the mitochondrial energy metabolism, oxidative phosphorylation, is important for the process of stem cell differentiation. Interestingly, a recent study reported that salicylate promotes mitochondrial biogenesis by regulating the expression of $PGC-1{\alpha}$ in murine cells. However, the possible effects of salicylate on osteogenic differentiation through increased mitochondrial biogenesis in stem cells remain unknown. Thus, here we investigated whether salicylate could influence osteogenic differentiation and mitochondrial biogenesis of periosteum-derived mesenchymal stem cells (POMSCs). We found that salicylate treatments of POMSCs undergoing osteogenic differentiation increased the activity of alkaline phosphatase, a well-known early marker of bone cell differentiation. In addition, we observed that mitochondrial mass was increased by salicylate treatments in POMSCs. Together, these results indicate that salicylate can enhance osteogenic differentiation and mitochondrial biogenesis in POMSCs. Therefore, the findings in this study suggest that small molecules augmenting mitochondrial function such as salicylate can be a novel modulator for osteogenic differentiation and regenerative medicine.

• Journal of Nutrition and Health
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• v.57 no.1
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• pp.53-64
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• 2024

Purpose: Mitochondria play a crucial role in preserving skeletal muscle mass, and damage to mitochondria leads to muscle mass loss. This study investigated the effects of oxypeucedanin hydrate, a furanocoumarin isolated from Angelica dahurica radix, on myogenesis and mitochondrial function in vitro and in zebrafish models. Methods: C2C12 myotubes cultured in media containing 0.1, 1, 10, or 100 ng/mL oxypeucedanin hydrate were immunostained with myosin heavy chain (MHC), and then multinucleated MHC-positive cells were counted. The expressions of markers related to muscle differentiation, muscle protein degradation, and mitochondrial function were determined by quantitative reverse transcription polymerase chain reaction. To investigate the effects of oxypeucedanin hydrate on mitochondrial dysfunction, Tg(Xla.Eef1a1:mito-EGFP) zebrafish embryos were treated with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without oxypeucedanin hydrate and analyzed for mito-EGFP intensity and mitochondrial length. Results: Oxypeucedanin hydrate significantly increased MHC-positive multinucleated myotubes (≥ 3 nuclei) and increased the expression of the myogenic marker myosin heavy chain 4. However, it decreased the expressions of muscle-specific RING finger protein 1 and muscle atrophy f-box (markers of muscle protein degradation). Furthermore, oxypeucedanin hydrate enhanced the expressions of markers of mitochondrial biogenesis (peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, transcription factor a mitochondrial, succinate dehydrogenase complex flavoprotein subunit A, and cytochrome c oxidase subunit 1) and mitochondrial fusion (optic atrophy 1). However, it reduced the expression of dynamin-related protein 1 (a mitochondrial fission regulator). Consistently, oxypeucedanin hydrate reduced FOLFIRI-induced mitochondrial dysfunction in the skeletal muscles of zebrafish embryos. Conclusion: The study indicates that oxypeucedanin hydrate promotes myogenesis by improving mitochondrial function, and thus, suggests oxypeucedanin hydrate has potential use as a nutritional supplement that improves muscle mass and function.