Dysregulation of IRP1-mediated iron metabolism causes gamma ray-specific radioresistance in leukemia cells
| Autor: | Aneesh Sheth, David A. Scheinberg, Kurtis J. Haro |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cancer Treatment
lcsh:Medicine Protein oxidation Biochemistry Radiation Tolerance Small hairpin RNA Hematologic Cancers and Related Disorders 0302 clinical medicine DNA Breaks Double-Stranded lcsh:Science Genetics 0303 health sciences Multidisciplinary Radiochemistry Cell Death Physics Hematology Radiation Exposure Alpha Particles Cell biology Chemistry Oncology 030220 oncology & carcinogenesis Medicine Research Article Programmed cell death DNA repair DNA damage Radiation Biophysics Nuclear Chemistry Iron Biophysics Radiation Therapy Biology 03 medical and health sciences Radioresistance Cell Line Tumor Leukemias Humans Iron Regulatory Protein 1 030304 developmental biology Radiation Chemistry lcsh:R Oxygen transport Radiobiology Cancers and Neoplasms Deinococcus radiodurans Dose-Response Relationship Radiation biology.organism_classification Radiation Effects Metabolism Gamma Rays lcsh:Q |
| Zdroj: | PLoS ONE, Vol 7, Iss 11, p e48841 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Iron is required for nearly all organisms, playing important roles in oxygen transport and many enzymatic reactions. Excess iron, however, can be cytotoxic. Emerging evidence suggests that radioresistance can be achieved in lower organisms by the protection of proteins, but not DNA, immediately following ionizing radiation (IR) exposure, allowing for improved DNA repair. One potential mechanism for protein protection is controlling and limiting the amount of free iron in cells, as has been demonstrated in the extremophile Deinococcus Radiodurans, reducing the potential for oxidative damage to proteins during exposure to IR. We found that iron regulatory protein 1 (IRP1) expression was markedly reduced in human myeloid leukemia HL60 cells resistant to low linear energy transfer (LET) gamma rays, but not to high LET alpha particles. Stable knockdown of IRP1 by short-hairpin RNA (shRNA) interference in radiosensitive parental cells led to radioresistance to low LET IR, reduced intracellular Fenton chemistry, reduced protein oxidation, and more rapid DNA double-strand break (DSB) repair. The mechanism of radioresistance appeared to be related to attenuated free radical-mediated cell death. Control of intracellular iron by IRPs may be a novel radioresistance mechanism in mammalian cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|