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Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin complex.
Biochem Biophys Res Commun. 2005 Aug 26; 334(2):298-305.BB

Abstract

Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on apoptosis. Superoxide dismutase (SOD) mimetics have been shown to be protective against cell injury caused by reactive oxygen species. We investigated the effects of the manganese (III) tetrakis(N-methyl-2-pyridyl)porphyrin (MnTMPyP), a cell-permeable SOD mimetic, on ionizing radiation-induced apoptosis. Upon exposure to 2 Gy of gamma-irradiation, there was a distinct difference between the control cells and the cells pre-treated with 5 microM MnTMPyP for 2 h with regard to apoptotic parameters, cellular redox status, mitochondria function, and oxidative damage to cells. MnTMPyP effectively suppressed morphological evidence of apoptosis and DNA fragmentation in U937 cells exposed to ionizing radiation. The [GSSG]/[GSH+GSSG] ratio and the generation of intracellular reactive oxygen species were higher and the [NADPH]/[NADP(+)+NADPH] ratio was lower in control cells compared to MnTMPyP-treated cells. The ionizing radiation-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of reactive oxygen species, and the reduction of ATP production were significantly higher in control cells compared to MnTMPyP-treated cells. MnTMPyP pre-treated cells showed significant inhibition of apoptotic features such as activation of caspase-3, up-regulation of Bax and p53, and down-regulation of Bcl-2 compared to control cells upon exposure to ionizing radiation. This study indicates that MnTMPyP may play an important role in regulating the apoptosis induced by ionizing radiation presumably through scavenging of reactive oxygen species.

Authors+Show Affiliations

School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16002045

Citation

Lee, Jin Hyup, et al. "Regulation of Ionizing Radiation-induced Apoptosis By a Manganese Porphyrin Complex." Biochemical and Biophysical Research Communications, vol. 334, no. 2, 2005, pp. 298-305.
Lee JH, Lee YM, Park JW. Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin complex. Biochem Biophys Res Commun. 2005;334(2):298-305.
Lee, J. H., Lee, Y. M., & Park, J. W. (2005). Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin complex. Biochemical and Biophysical Research Communications, 334(2), 298-305.
Lee JH, Lee YM, Park JW. Regulation of Ionizing Radiation-induced Apoptosis By a Manganese Porphyrin Complex. Biochem Biophys Res Commun. 2005 Aug 26;334(2):298-305. PubMed PMID: 16002045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin complex. AU - Lee,Jin Hyup, AU - Lee,You Mie, AU - Park,Jeen-Woo, PY - 2005/05/30/received PY - 2005/06/01/accepted PY - 2005/7/9/pubmed PY - 2005/9/27/medline PY - 2005/7/9/entrez SP - 298 EP - 305 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 334 IS - 2 N2 - Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on apoptosis. Superoxide dismutase (SOD) mimetics have been shown to be protective against cell injury caused by reactive oxygen species. We investigated the effects of the manganese (III) tetrakis(N-methyl-2-pyridyl)porphyrin (MnTMPyP), a cell-permeable SOD mimetic, on ionizing radiation-induced apoptosis. Upon exposure to 2 Gy of gamma-irradiation, there was a distinct difference between the control cells and the cells pre-treated with 5 microM MnTMPyP for 2 h with regard to apoptotic parameters, cellular redox status, mitochondria function, and oxidative damage to cells. MnTMPyP effectively suppressed morphological evidence of apoptosis and DNA fragmentation in U937 cells exposed to ionizing radiation. The [GSSG]/[GSH+GSSG] ratio and the generation of intracellular reactive oxygen species were higher and the [NADPH]/[NADP(+)+NADPH] ratio was lower in control cells compared to MnTMPyP-treated cells. The ionizing radiation-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of reactive oxygen species, and the reduction of ATP production were significantly higher in control cells compared to MnTMPyP-treated cells. MnTMPyP pre-treated cells showed significant inhibition of apoptotic features such as activation of caspase-3, up-regulation of Bax and p53, and down-regulation of Bcl-2 compared to control cells upon exposure to ionizing radiation. This study indicates that MnTMPyP may play an important role in regulating the apoptosis induced by ionizing radiation presumably through scavenging of reactive oxygen species. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/16002045/Regulation_of_ionizing_radiation_induced_apoptosis_by_a_manganese_porphyrin_complex_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(05)01217-9 DB - PRIME DP - Unbound Medicine ER -