title: Cadmium induced radioadaptive response via an ATM-independent H(2)S/cystathionine γ-lyase modulation.
abstract: The combined exposure to environmental toxicants such as heavy metals and radiation is an important research area in health protection. Here we explored cadmium induced radioadaptive response (RAR) and investigated the role of hydrogen sulfide (H(2)S) and ATM kinase in this response. Our data showed that the cadmium ions with a sub-lethal concentration could induce RAR in Chang liver cells towards subsequent γ-irradiation and this response could be abrogated by DL-propargylglycine (PPG), the endogenous H(2)S synthetase inhibitor of cystathionine γ-lyase (CSE), but not by aminooxyacetic acid (AOAA), the inhibitor of cystathionine β-synthase (CBS). Moreover, the pretreatment of cells with NaHS also stimulated cellular adaptive response to radiation. Both cadmium treatment and irradiation up-regulated the expression of CSE protein in a time-dependent manner but had no influence on the expression of CBS protein. In the primed cells, the time course of CBS expression showed no significant difference with the cells treated with 2Gy irradiation alone, however, the CSE expression was easier to reach the maximum level, indicating a more efficient H(2)S production by CSE. Moreover, the cadmium-induced RAR was totally suppressed by KU-55933, a specific ATM inhibitor that did not change the CSE expression after radiation. However, exogenous H(2)S decreased the phosphorylation level of radiation-induced ATM. In conclusion, the present results demonstrate firstly that H(2)S is involved in the cadmium induced cross-adaptive response to challenging radiation. CSE, rather than CBS, may mainly responsible for the H(2)S production during this RAR which may also be mediated by ATM pathway. However, the activation of CSE is independent of ATM but could negatively regulate the phosphorylation of ATM.
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Dexiao
authors.initials: D
authors.lastname: Yuan
authors.forename: Jianghong
authors.initials: J
authors.lastname: Zhang
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000528:radiation effects*; D064007:Ataxia Telangiectasia Mutated Proteins; D002104:Cadmium / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000494:pharmacology*; D002460:Cell Line; D003542:Cystathionine gamma-Lyase / Q000378:metabolism / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D002104:Cadmium; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide