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Attenuation of UV-induced apoptosis by coenzyme Q10 in human cells harboring large-scale deletion of mitochondrial DNA.
Ann N Y Acad Sci. 2005 May; 1042:429-38.AN

Abstract

Chronic progressive external ophthalmoplegia (CPEO) syndrome is one of the mitochondrial diseases caused by large-scale deletions in mitochondrial DNA (mtDNA) that impair the respiratory function of mitochondria and result in decreased production of ATP in affected tissues. In order to investigate whether CPEO-associated mtDNA mutations (i.e., 4,366-bp and 4,977-bp large-scale deletions) render human cells more vulnerable to apoptosis, we constructed cybrids carrying the deleted mtDNA. Assays for cell viability, DNA fragmentation, cytochrome c release, and caspase 3 activation revealed that UV irradiation at 20 J/m2 triggered apoptosis in all the cybrids. This treatment also produced elevated intracellular levels of reactive oxygen species (ROS). The rate of UV-induced cell death was more pronounced in the cybrids harboring mtDNA deletions than in the control cybrid with wild-type mtDNA. Subsequently, we evaluated the effect of coenzyme Q10 on the UV-triggered apoptosis. The results showed that after pretreatment of the cybrids with 100 microM coenzyme Q10 the UV-induced cell damage (i.e., ROS production and activation of caspase 3) was significantly reduced. Taken together, these findings suggest that large-scale deletions of mtDNA increased the susceptibility of human cells to the UV-triggered apoptosis and that coenzyme Q10 mitigated the damage; hence, it might potentially serve as a therapeutic agent to treat mitochondrial diseases resulting from mtDNA deletions.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15965089

Citation

Lee, Cheng-Feng, et al. "Attenuation of UV-induced Apoptosis By Coenzyme Q10 in Human Cells Harboring Large-scale Deletion of Mitochondrial DNA." Annals of the New York Academy of Sciences, vol. 1042, 2005, pp. 429-38.
Lee CF, Liu CY, Chen SM, et al. Attenuation of UV-induced apoptosis by coenzyme Q10 in human cells harboring large-scale deletion of mitochondrial DNA. Ann N Y Acad Sci. 2005;1042:429-38.
Lee, C. F., Liu, C. Y., Chen, S. M., Sikorska, M., Lin, C. Y., Chen, T. L., & Wei, Y. H. (2005). Attenuation of UV-induced apoptosis by coenzyme Q10 in human cells harboring large-scale deletion of mitochondrial DNA. Annals of the New York Academy of Sciences, 1042, 429-38.
Lee CF, et al. Attenuation of UV-induced Apoptosis By Coenzyme Q10 in Human Cells Harboring Large-scale Deletion of Mitochondrial DNA. Ann N Y Acad Sci. 2005;1042:429-38. PubMed PMID: 15965089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuation of UV-induced apoptosis by coenzyme Q10 in human cells harboring large-scale deletion of mitochondrial DNA. AU - Lee,Cheng-Feng, AU - Liu,Chun-Yi, AU - Chen,Shu-Mei, AU - Sikorska,Marianna, AU - Lin,Chen-Yu, AU - Chen,Tzu-Ling, AU - Wei,Yau-Huei, PY - 2005/6/21/pubmed PY - 2006/9/12/medline PY - 2005/6/21/entrez SP - 429 EP - 38 JF - Annals of the New York Academy of Sciences JO - Ann. N. Y. Acad. Sci. VL - 1042 N2 - Chronic progressive external ophthalmoplegia (CPEO) syndrome is one of the mitochondrial diseases caused by large-scale deletions in mitochondrial DNA (mtDNA) that impair the respiratory function of mitochondria and result in decreased production of ATP in affected tissues. In order to investigate whether CPEO-associated mtDNA mutations (i.e., 4,366-bp and 4,977-bp large-scale deletions) render human cells more vulnerable to apoptosis, we constructed cybrids carrying the deleted mtDNA. Assays for cell viability, DNA fragmentation, cytochrome c release, and caspase 3 activation revealed that UV irradiation at 20 J/m2 triggered apoptosis in all the cybrids. This treatment also produced elevated intracellular levels of reactive oxygen species (ROS). The rate of UV-induced cell death was more pronounced in the cybrids harboring mtDNA deletions than in the control cybrid with wild-type mtDNA. Subsequently, we evaluated the effect of coenzyme Q10 on the UV-triggered apoptosis. The results showed that after pretreatment of the cybrids with 100 microM coenzyme Q10 the UV-induced cell damage (i.e., ROS production and activation of caspase 3) was significantly reduced. Taken together, these findings suggest that large-scale deletions of mtDNA increased the susceptibility of human cells to the UV-triggered apoptosis and that coenzyme Q10 mitigated the damage; hence, it might potentially serve as a therapeutic agent to treat mitochondrial diseases resulting from mtDNA deletions. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/15965089/Attenuation_of_UV_induced_apoptosis_by_coenzyme_Q10_in_human_cells_harboring_large_scale_deletion_of_mitochondrial_DNA_ L2 - https://doi.org/10.1196/annals.1338.036 DB - PRIME DP - Unbound Medicine ER -