title: YES1 activation elicited by heat stress is anti-apoptotic in mouse pachytene spermatocytes.
abstract: Deregulated expression of protein tyrosine phosphorylation has been implicated in testicular response to different stimuli. Herein, YES1, a nonreceptor protein tyrosine kinase, was found to be significantly up-regulated in pachytene spermatocytes (PS) during early recovery from a transient testicular heat stress. Coculture of PS with Sertoli cells (SCs) could enhance the hyperthermia-induced YES1 activation, indicative of a positive regulation of the paracrine signaling. Moreover, SU6656, a selective YES1 inhibitor, was shown to effectively block YES1 activity, thereafter resulting in a dramatic increase of heat stress-induced apoptosis in primary cultured PS. Mechanistically, the antiapoptotic effect of YES1 activation in response to testicular heat insult may mediate via the regulation of extracellular signal-regulated kinase (ERK)/metastasis-associated 1 (MTA1) cascade. From a clinical standpoint, a notably higher level of YES1 expression was observed in the pathological testis from varicocele patients as compared to a negligible staining in the control group. Taken together, our present results provide the first evidence that the YES1/ERK/MTA1/p53 cascade may serve as a naturally occurring, indispensable self-defensive mechanism maintaining apoptotic balance during meiotic heat stress. Our study may have also partially answered the question of how activation of signal pathways at the cell membrane surface interacts with the key regulatory events occurring in the nucleus during testicular heat shock.
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liang
authors.forename: Yushu
authors.initials: Y
authors.lastname: Dong
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002478:Cells, Cultured; D015870:Gene Expression; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049471:Pachytene Stage / Q000235:genetics*; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics*; D012097:Repressor Proteins; D013090:Spermatocytes / Q000166:cytology / Q000502:physiology*; D013737:Testis / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: C503336:Mta1 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051575:Proto-Oncogene Proteins c-yes; C496639:Yes1 protein, mouse
keywords: apoptosis; heat stress; meiosis; pachytene spermatocyte; tyrosine kinase