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Involvement of endoplasmic reticulum stress in apoptosis of testicular cells induced by low-dose radiation

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Summary

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. H2O2 and NO concentrations, and Ca2+-ATPase activity were detected by biochemical assays, the calcium ion concentration ([Ca2+]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 [Ca2+]i and Ca2+-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.

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Authors and Affiliations

  1. Key Laboratory of Radiobiology of Ministry of Health, School of Public Health, Jilin University, Changchun, 130021, China

    Zhi-cheng Wang  (王志成), Jian-feng Wang  (王剑锋), Yan-bo Li  (李艳博), Yang Liu  (刘 扬), Fang Fang  (方 芳) & Shou-liang Gong  (龚守良)

  2. School of Public Health and Family Medicine, Capital Medical University, Beijing, 100069, China

    Yan-bo Li  (李艳博) & Cai-xia Guo  (郭彩霞)

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  1. Zhi-cheng Wang  (王志成)
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  2. Jian-feng Wang  (王剑锋)
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  3. Yan-bo Li  (李艳博)
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  4. Cai-xia Guo  (郭彩霞)
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  5. Yang Liu  (刘 扬)
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  6. Fang Fang  (方 芳)
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  7. Shou-liang Gong  (龚守良)
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Corresponding authors

Correspondence to Fang Fang  (方 芳) or Shou-liang Gong  (龚守良).

Additional information

Both authors contributed equally to this work.

This work was supported by the grants from the National Natural Science Foundation of China (No. 30970681) and Basic Research and Operating Expenses of Jilin University (No. 200903116).

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Wang, Zc., Wang, Jf., Li, Yb. et al. Involvement of endoplasmic reticulum stress in apoptosis of testicular cells induced by low-dose radiation. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 551–558 (2013). https://doi.org/10.1007/s11596-013-1157-0

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  • DOI: https://doi.org/10.1007/s11596-013-1157-0

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