Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin complex.
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.
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.
Jin Hyup
JH
Lee
You Mie
YM
Lee
Jeen-Woo
JW
Park
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects*; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology; D020298:U937 Cells
D008665:Metalloporphyrins; D011837:Radiation-Protective Agents; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D004247:DNA