PGAM1 knockdown is associated with busulfan‑induced hypospermatogenesis and spermatogenic cell apoptosis

Zhao,Yuanshu; Zhang,Shoubo

doi:10.3892/mmr.2019.9930

PGAM1 knockdown is associated with busulfan‑induced hypospermatogenesis and spermatogenic cell apoptosis

Authors:
- Yuanshu Zhao
- Shoubo Zhang
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Affiliations: Functional Experiment Center, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China, Center for Reproductive Medicine, Guangdong Armed Police Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510507, P.R. China
Published online on: February 4, 2019 https://doi.org/10.3892/mmr.2019.9930
Pages: 2497-2502
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Phosphoglycerate mutase 1 (PGAM1) is reported to be involved in spermatogenic dysfunction. However, the association between PGAM1 and busulfan‑induced hypospermatogenesis and spermatogenic cell apoptosis remains unclear. The aim of the current study was to investigate the association between PGAM1 expression and busulfan‑induced hypospermatogenesis, and the effect of PGAM1 expression on spermatogenic cell apoptosis. PGAM1 expression was detected in mouse models of busulfan‑induced hypospermatogenesis by western blotting, reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry. Then, spermatogenic cell apoptosis in mouse models of busulfan‑induced hypospermatogenesis was assessed by TUNEL assay. The effect and potential mechanism of PGAM1 downregulation on spermatogenic cells were further investigated. The results indicated that PGAM1 expression was significantly downregulated in the mouse models of busulfan‑induced hypospermatogenesis, compared with those with normal spermatogenesis (P<0.05). Furthermore, the TUNEL assay revealed that the apoptosis of spermatogenic cells was accelerated in the mouse model of busulfan‑induced hypospermatogenesis. In addition, PGAM1 knockdown promoted the apoptosis of spermatogenic cells in vitro, which was associated with the P53/Caspase 3/Caspase 6/Caspase 9 signaling pathway. In conclusion, these data indicate that PGAM1 knockdown is associated with busulfan‑induced hypospermatogenesis and contributes to spermatogenic cell apoptosis by regulating the P53/Caspase 3/Caspase 6/Caspase 9 signaling pathway.

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1	Jiang X, Sun Q, Li H, Li K and Ren X: The role of phosphoglycerate mutase 1 in tumor aerobic glycolysis and its potential therapeutic implications. Int J Cancer. 135:1991–1996. 2014. View Article : Google Scholar : PubMed/NCBI
2	Jacobowitz DM, Jozwik C, Fukuda T and Pollard HB: Immunohistochemical localization of phosphoglycerate mutase in capillary endothelium of the brain and periphery. Microvasc Res. 76:89–93. 2008. View Article : Google Scholar : PubMed/NCBI
3	Betrán E, Wang W, Jin L and Long M: Evolution of the phosphoglycerate mutase processed gene in human and chimpanzee revealing the origin of a new primate gene. Mol Biol Evol. 19:654–663. 2002. View Article : Google Scholar : PubMed/NCBI
4	Gao H, Yu B, Yan Y, Shen J, Zhao S, Zhu J, Qin W and Gao Y: Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis. J Neurosurg. 118:846–853. 2013. View Article : Google Scholar : PubMed/NCBI
5	Bührens RI, Amelung JT, Reymond MA and Beshay M: Protein expression in human non-small cell lung cancer: A systematic database. Pathobiology. 76:277–285. 2009. View Article : Google Scholar : PubMed/NCBI
6	Durany N, Joseph J, Jimenez OM, Climent F, Fernández PL, Rivera F and Carreras J: Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes in breast carcinoma. Br J Cancer. 82:20–27. 2000. View Article : Google Scholar : PubMed/NCBI
7	Turhani D, Krapfenbauer K, Thurnher D, Langen H and Fountoulakis M: Identification of differentially expressed, tumor-associated proteins in oral squamous cell carcinoma by proteomic analysis. Electrophoresis. 27:1417–1423. 2006. View Article : Google Scholar : PubMed/NCBI
8	Ren F, Wu H, Lei Y, Zhang H, Liu R, Zhao Y, Chen X, Zeng D, Tong A, Chen L, et al: Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma. Mol Cancer. 9:812010. View Article : Google Scholar : PubMed/NCBI
9	Peng XC, Gong FM, Chen Y, Qiu M, Cheng K, Tang J, Ge J, Chen N, Zeng H and Liu JY: Proteomics identification of PGAM1 as a potential therapeutic target for urothelial bladder cancer. J Proteomics. 132:85–92. 2016. View Article : Google Scholar : PubMed/NCBI
10	Xu Z, Gong J, Wang C, Wang Y, Song Y, Xu W, Liu Z and Liu Y: The diagnostic value and functional roles of phosphoglycerate mutase 1 in glioma. Oncol Rep. 36:2236–2244. 2016. View Article : Google Scholar : PubMed/NCBI
11	Zhang D, Jin N, Sun W, Li X, Liu B, Xie Z, Qu J, Xu J, Yang X, Su Y, et al: Phosphoglycerate mutase 1 promotes cancer cell migration independent of its metabolic activity. Oncogene. 36:2900–2909. 2017. View Article : Google Scholar : PubMed/NCBI
12	Zhang D, Wu H, Zhang X, Ding X, Huang M, Geng M, Li H and Xie Z: Phosphoglycerate mutase 1 predicts the poor prognosis of oral squamous cell carcinoma and is associated with cell migration. J Cancer. 8:1943–1951. 2017. View Article : Google Scholar : PubMed/NCBI
13	Qu J, Sun W, Zhong J, Lv H, Zhu M, Xu J, Jin N, Xie Z, Tan M, Lin SH, et al: Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells. J Cell Biol. 216:409–424. 2017. View Article : Google Scholar : PubMed/NCBI
14	Kimura A, Sakurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Tanaka R, Takemura M, Seishima M and Inuzuka T: High prevalence of autoantibodies against phosphoglycerate mutase 1 in patients with autoimmune central nervous system diseases. J Neuroimmunol. 219:105–108. 2010. View Article : Google Scholar : PubMed/NCBI
15	Zhang S, Zhao Y, Lei B, Li C and Mao X: PGAM1 is Involved in spermatogenic dysfunction and affects cell proliferation, apoptosis, and migration. Reprod Sci. 22:1236–1242. 2015. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Lei B, Zhou X, Lv D, Wan B, Wu H, Zhong L, Shu F and Mao X: Apoptotic and nonapoptotic function of caspase 7 in spermatogenesis. Asian J Androl. 19:47–51. 2017.PubMed/NCBI
18	Robin G, Boitrelle F, Leroy X, Peers MC, Marcelli F, Rigot JM and Mitchell V: Assessment of azoospermia and histological evaluation of spermatogenesis. Ann Pathol. 30:182–195. 2010.(In French). View Article : Google Scholar : PubMed/NCBI
19	Cheng YS, Lu CW, Lin TY, Lin PY and Lin YM: Causes and clinical features of infertile men with nonobstructive azoospermia and histopathologic diagnosis of hypospermatogenesis. Urology. 105:62–68. 2017. View Article : Google Scholar : PubMed/NCBI
20	Takagi S, Itoh N, Kimura M, Sasao T and Tsukamoto T: Spermatogonial proliferation and apoptosis in hypospermatogenesis associated with nonobstructive azoospermia. Fertil Steril. 76:901–907. 2001. View Article : Google Scholar : PubMed/NCBI
21	Jaiswal D, Trivedi S, Agrawal NK and Singh K: Dysregulation of apoptotic pathway candidate genes and proteins in infertile azoospermia patients. Fertil Steril. 104:736–743.e6. 2015. View Article : Google Scholar : PubMed/NCBI
22	Hegazy R, Hegazy A, Ammar M and Salem E: Immunohistochemical measurement and expression of Mcl-1 in infertile testes. Front Med. 9:361–367. 2015. View Article : Google Scholar : PubMed/NCBI
23	Han K, Seo HW, Oh Y, Kang I, Park C, Han JH, Kim SH and Chae C: Pathogenesis of type 1 (European genotype) porcine reproductive and respiratory syndrome virus in male gonads of infected boar. Vet Res Commun. 37:155–162. 2013. View Article : Google Scholar : PubMed/NCBI
24	Napoletano F, Gibert B, Yacobi-Sharon K, Vincent S, Favrot C, Mehlen P, Girard V, Teil M, Chatelain G, Walter L, et al: p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis. PLoS Genet. 13:e10070242017. View Article : Google Scholar : PubMed/NCBI
25	Li T, Liu X, Jiang L, Manfredi J, Zha S and Gu W: Loss of p53-mediated cell-cycle arrest, senescence and apoptosis promotes genomic instability and premature aging. Oncotarget. 7:11838–11849. 2016.PubMed/NCBI
26	Duan P, Hu C, Butler HJ, Quan C, Chen W, Huang W, Tang S, Zhou W, Yuan M, Shi Y, et al: 4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling. Environ Toxicol. 32:739–753. 2017. View Article : Google Scholar : PubMed/NCBI
27	Chen D, Zheng W, Lin A, Uyhazi K, Zhao H and Lin H: Pumilio 1 suppresses multiple activators of p53 to safeguard spermatogenesis. Curr Biol. 22:420–425. 2012. View Article : Google Scholar : PubMed/NCBI
28	Zhao Y, Tan Y, Dai J, Li B, Guo L, Cui J, Wang G, Shi X, Zhang X, Mellen N, et al: Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice. Toxicol Lett. 200:100–106. 2011. View Article : Google Scholar : PubMed/NCBI
29	Logue SE and Martin SJ: Caspase activation cascades in apoptosis. Biochem Soc Trans. 36:1–9. 2008. View Article : Google Scholar : PubMed/NCBI
30	Das J, Ghosh J, Manna P and Sil PC: Taurine protects rat testes against doxorubicin-induced oxidative stress as well as p53, Fas and caspase 12-mediated apoptosis. Amino Acids. 42:1839–1855. 2012. View Article : Google Scholar : PubMed/NCBI