Cigarette Smoking Exposure Alters Pebp1 DNA Methylation and Protein Profile Involved in MAPK Signaling Pathway in Mice Testis

被引:35
作者
Xu, Wangjie [1 ]
Fang, Peng [1 ]
Zhu, Zijue [1 ]
Dai, Jingbo [1 ]
Nie, Dongsheng [1 ]
Chen, Zhong [2 ]
Qin, Qiaojing [3 ]
Wang, Lianyun [1 ]
Wang, Zhaoxia [1 ]
Qiao, Zhongdong [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Life Sci & Technol, Shanghai 200240, Peoples R China
[2] Shanghai Jiao Tong Univ, Dept Urol, Shanghai Peoples Hosp 6, Shanghai 200030, Peoples R China
[3] Fudan Univ, Dept Nephrol, Shanghai Peoples Hosp 5, Shanghai 200433, Peoples R China
基金
中国国家自然科学基金;
关键词
cigarette smoking; DNA methylation; MALDI-TOF-MS; male infertility; MAPK; PEBP1; proteomics; spermatogenesis; testis; OXIDATIVE STRESS; SPERMATOGONIAL PROLIFERATION; FERTILIZING-CAPACITY; HUMAN SPERM; IN-VITRO; KINASE; ACTIVATION; EXPRESSION; CANCER; DAMAGE;
D O I
10.1095/biolreprod.113.111245
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Many studies have addressed the role of cigarette smoking on semen quality, but the exact mechanisms remain inconclusive. To evaluate the detrimental effects of smoking on the spermatogenesis process, we initially screened and investigated 31 differentially expressed proteins extracted from the testes of mice exposed daily to cigarette smoke using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry analysis. Data mining analysis showed that these 31 proteins were categorized into five functional clustering groups: metabolic process, cell growth and/or maintenance, RNA and protein processing, stress response, and spermatogenesis. Additionally, 23 of 31 proteins were involved in a main pathway network, including Pkc (s), ERK1/2, Akt, and NF-kappaB, which are known to be involved in cell communication, proliferation, and differentiation. Interestingly, among the 31 proteins, a spermatogenesis-associated protein, phosphatidylethanolamine-binding protein 1 (PEBP1), was especially expressed in serial sections of spermatids of spermiogenesis and interacted with ERKs. The bisulfite sequencing result showed four CpGs near the Pebp1 transcriptional start site were largely methylated in the treated group. A 5-aza-2'-deoxycytidine treatment on GC-1 spg cells reversed the hypermethylation status and elevated both Pebp1 mRNA and protein expression levels. ERK1/2 phosphorylation levels were also increased with upregulation of Pebp1 expression in GC-1 spg cells. In conclusion, protein profile in testes could be altered by cigarette smoking. Moreover, we also suggest that epigenetic Pebp1 inactivation may affect activation of ERK, and it could impair spermatogenesis of mice. Our data could provide further insight into the mechanisms of spermatogenesis.
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页数:11
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