title: Involvement of endoplasmic reticulum stress in apoptosis of testicular cells induced by low-dose radiation.
abstract: The study examined the role of endoplasmic reticulum stress (ERS) and signaling pathways of inositol-requiring enzyme-1 (IRE1), RNA-activated protein kinase-like ER kinase (PERK) and activating transcription factor-6 (ATF6) in apoptosis of mouse testicular cells treated with low-dose radiation (LDR). In the dose-dependent experiment, the mice were treated with whole-body X-ray irradiation at different doses (25, 50, 75, 100 or 200 mGy) and sacrificed 12 h later. In the time-dependent experiment, the mice were exposed to 75 mGy X-ray irradiation and killed at different time points (3, 6, 12, 18 or 24 h). Testicular cells were harvested for experiments. H(2)O(2) and NO concentrations, and Ca(2+)-ATPase activity were detected by biochemical assays, the calcium ion concentration ([Ca(2+)]i) by flow cytometry using fluo-3 probe, and GRP78 mRNA and protein expressions by quantitative real-time RT-PCR (qRT-PCR) and Western blotting, respectively. The mRNA expressions of S-XBP1, JNK, caspase-12 and CHOP were measured by qRT-PCR, and the protein expressions of IRE1α, S-XBP1, p-PERK, p-eIF2α, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP by Western blotting. The results showed that the concentrations of H2O2 and NO, the mRNA expressions of GRP78, S-XBP1, JNK, caspase-12 and CHOP, and the protein expressions of GRP78, S-XBP1, IRE1α, p-PERK, p-eIF2α, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP were significantly increased in a time- and dose-dependent manner after LDR. But the [Ca(2+)]i and Ca(2+)-ATPase activities were significantly decreased in a time- and dose-dependent manner. It was concluded that the ERS, regulated by IRE1, PERK and ATF6 pathways, is involved in the apoptosis of testicular cells in LDR mice, which is associated with ERS-apoptotic signaling molecules of JNK, caspase-12 and CHOP.
authors.affiliation: Key Laboratory of Radiobiology of Ministry of Health, School of Public Health, Jilin University, Changchun, 130021, China.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Wang
authors.affiliation: Key Laboratory of Radiobiology of Ministry of Health, School of Public Health, Jilin University, Changchun, 130021, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Wang
authors.affiliation: Key Laboratory of Radiobiology of Ministry of Health, School of Public Health, Jilin University, Changchun, 130021, China.|School of Public Health and Family Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Li
authors.affiliation: School of Public Health and Family Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Guo
authors.affiliation: Key Laboratory of Radiobiology of Ministry of Health, School of Public Health, Jilin University, Changchun, 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Radiobiology of Ministry of Health, School of Public Health, Jilin University, Changchun, 130021, China. jfwang@jlu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Key Laboratory of Radiobiology of Ministry of Health, School of Public Health, Jilin University, Changchun, 130021, China. gongsl@163.com.
authors.forename: Shou-Liang
authors.initials: SL
authors.lastname: Gong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D011827:Radiation; D013737:Testis / Q000502:physiology* / Q000528:radiation effects*
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