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Elevated Mitochondrial DNA Copy Number and POL-γ Expression but Decreased Expression of TFAM in Murine Intestine Following Therapeutic Dose Irradiation

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 701))

Abstract

Mitochondria play pivotal roles in cellular handling of oxygen and in apoptosis, the ordered suicide response of cells to irradiation. The involvement of expression products from the 16.5 kb human mitochondrial genome in these activities has been studied widely. However, little is known about effects of irradiation on mammalian mitochondrial DNA (mtDNA). The relative lack of mtDNA repair mechanisms compared with nuclear DNA (nDNA) predicts particular vulnerability to irradiation. Using a technique developed to ascertain mtDNA:nDNA ratios, we previously showed that this ratio increases dramatically inmurine small bowel within 48 hours followingwhole body irradiation. We now report that those levels continue to rise for four days and remain elevated at close to that level beyond 30 days after 5 Gy of irradiation.We further demonstrate that levels of the mtDNA-specific DNA polymerase-γ (Pol-γ ) also show a sharp and sustained increase during this time course after a 2-Gy dose. Paradoxically, transcription factor A (TFAM), exhibited the directly opposite response.

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References

  1. Purkayastha SJ, Milligan R, and Bernhard WA (2007) On the chemical yield of base lesions, strand breaks, and clustered damage generated in plasmid DNA by the direct effect of x rays. Radiat Res 168:357-366

    Article  PubMed  CAS  Google Scholar 

  2. Yakes FM, and Van Houten B (1997)Mitochondrial DNAdamage ismore extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 94:514-519

    Article  PubMed  CAS  Google Scholar 

  3. Iliakis G, Wang H, Perrault AR, et al. (2004) Mechanisms of DNA double strand break repair and chromosome aberration formation. Cytogenet Genome Res 104:14-20

    Article  PubMed  CAS  Google Scholar 

  4. Larsen NB, Rasmussen M, and Rasmussen LJ (2005) Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5:89-108

    Article  PubMed  CAS  Google Scholar 

  5. Malakhova L, Bezlepkin VG, Antipova V, et al. (2005) The increase inmitochondrial DNAcopy number in the tissues of γ -irradiated mice. Cell Mol Biol Lett 10:721–732

    PubMed  CAS  Google Scholar 

  6. ZhangH,Maguire D, Swarts S, et al. (2009) Replication ofmurinemitochondrialDNAfollowing irradiation. Adv Exp Med Biol 645:43-48

    Article  Google Scholar 

  7. Pfaffl MW (2001) A new mathematical model for relative quantification in real time RT-PCR. Nuc Acids Res 29:e45

    Article  CAS  Google Scholar 

  8. Laemmli, UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-685

    Article  PubMed  CAS  Google Scholar 

  9. Denham JW, Hauer-Jensen M, Kron T, et al. (2000) Treatment-time-dependence models of early and delayed radiation injury in rat small intestine. Int J Radiat Biol Phys 48:871-887

    Article  CAS  Google Scholar 

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Correspondence to Hengshan Zhang .

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Zhang, H., Maguire, D.J., Zhang, M., Zhang, L., Okunieff, P. (2011). Elevated Mitochondrial DNA Copy Number and POL-γ Expression but Decreased Expression of TFAM in Murine Intestine Following Therapeutic Dose Irradiation. In: LaManna, J., Puchowicz, M., Xu, K., Harrison, D., Bruley, D. (eds) Oxygen Transport to Tissue XXXII. Advances in Experimental Medicine and Biology, vol 701. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7756-4_27

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