Earticle

초록

영어

Mitochondrial DNA (mtDNA) deletion is a well‐known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF‐1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)‐induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR‐90 human lung fibroblast cells. Young IMR‐90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2‐treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence‐associated β‐galactosidase (SA‐β‐gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF‐1 and TFAM in IMR‐90 cells. Similar results were also observed in old cells (PD 55) and H2O2‐treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N‐acetylcysteine (NAC) were examined. In irradiated and H2O2–treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA‐β‐gal activity, and recovered from decreased expressions of NRF‐1 and TFAM mRNA. These results suggest that ROS is a key cause of IR‐induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

목차

Abstract
 1. INTRODUCTION
 2. MATERIALS AND METHODS
 3. RESULTS AND DISCUSSION
 REFERENCES

키워드

저자

• Hyeon Soo Eom [ Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, Department of Biochemistry, College of Natural Sciences, Chungnam National University ]
• Uhee Jung [ Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute ] Corresponding author
• Sung-Kee Jo [ Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, ]
• Young Sang Kim [ Department of Biochemistry, College of Natural Sciences, Chungnam National University ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  방사선방어학회지 [Journal of Radiation Protection and Research]

• 간기

  계간

• pISSN

  2508-1888

• 수록기간

  1976~2026

• 등재여부

  KCI 등재,SCOPUS

• 십진분류

  KDC 559 DDC 629