Biomedical subjects

Yangyang Wang

Publications and source records attributed to Yangyang Wang.

4 recordsLinked to original sources

PubMed2006

Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint signaling in rat spermatocytes.

In somatic cells, integrity of cell division is safeguarded by the spindle checkpoint, a signaling cascade that delays the separation of sister chromatids in the presence of misaligned chromosomes. Aurora kinases play important roles in this process by promoting centrosome maturation, chromosome bi-orientation, spindle checkpoint signaling, and cytokinesis. To investigate the functions of Aurora kinases in male meiosis, we applied a small molecule Aurora inhibitor, ZM447439, to seminiferous tubules in vitro. Primary and secondary spermatocytes exposed to ZM447439 exhibit defects in the spindle morphology and fail to align their chromosomes at the metaphase plate. Moreover, the treated spermatocytes undergo a forced exit from the meiotic M-phase without cytokinesis. These results suggest that the activities of Aurora kinases are required for normal spindle assembly as well as for establishment and maintenance of proper microtubule-kinetochore attachments and spindle checkpoint signaling in male mammalian meiosis.

Animals↗

PubMed2005

The regulated expression of c-IAP1 and c-IAP2 during the rat seminiferous epithelial cycle plays a role in the protection of germ cells from Fas-mediated apoptosis.

The inhibitor of apoptosis proteins, c-IAP1 and c-IAP2, are highly expressed in rat testis and potentially play a regulatory role in testicular apoptosis. To better understand their functions during spermatogenesis, we have analyzed their spatio-temporal distribution in rat testis, how their expression is controlled by the paracrine stem-cell factor (SCF) and how they affect Fas-mediated apoptosis. Both c-IAP1 and c-IAP2 showed cycles of transcriptional expression, throughout the seminiferous epithelial cycle. c-IAP1 protein showed a diffuse nuclear distribution in type B spermatogonia, preleptotene, leptotene, and zygotene spermatocytes. In pachytene spermatocytes, c-IAP1 colocalized with SUMO-1 in the XY-body. c-IAP2 protein was cytoplasmic in spermatocytes, from stage VI pachytene onwards, round spermatids, elongated spermatids and Leydig cells. Its expression was upregulated by SCF. Inhibition of IAP activity resulted in a greater sensitivity of germ cells to Fas-mediated apoptosis. These results suggest an important role for IAPs in the regulation of spermatogenic apoptosis.

Animals↗

PubMed2004

Survivin expression in rat testis is upregulated by stem-cell factor.

The inhibitor of apoptosis protein BIRC-5/survivin plays roles in both apoptosis and the regulation of chromosome-segregation/cytokinesis during mitosis. As the population dynamics of male germ cells are regulated by both proliferation (mitosis and meiosis) and apoptotic culling, we hypothesized that BIRC-5/survivin could be central to the regulation of spermatogenesis. We have analyzed BIRC-5/survivin expression throughout the seminiferous epithelial cycle of the rat. BIRC-5/survivin RNA and protein exhibit rhythms of expression throughout the seminiferous epithelial cycle. The highest levels of expression were found, by immunohistochemistry and in situ hybridization, to occur during the long first meiotic prophase of spermatocytes. Cytoplasmic abundance declined at metaphase and reappeared at anaphase. Some BIRC-5/survivin expression was also found to occur in interstitial Leydig cells. BIRC-5/survivin protein levels were up-regulated in vitro by the paracrine, Stem-Cell Factor, that is known to regulate both proliferation and apoptosis of germ cells and Leydig cells.

Animals↗

PubMed2004

Tumor necrosis factor-alpha (TNF-alpha) promotes cell survival during spermatogenesis, and this effect can be blocked by infliximab, a TNF-alpha antagonist.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) has been shown to inhibit germ cell death in human seminiferous epithelium. In the present study, we wanted to explore the effects of TNF-alpha in the rat seminiferous epithelium and to study molecular mechanisms of germ cell apoptosis. Furthermore, the effects of infliximab were studied. Infliximab is a TNF-alpha antagonist used in autoimmune disorders, such as rheumatoid arthritis and Crohn's disease. METHODS: Rat seminiferous tubule segments were cultured in the presence and absence of TNF-alpha, infliximab and SN50, a NF-kappa B inhibitor. TUNEL-staining and cleaved caspase-3 immunohistochemistry combined with squash preparations of rat seminiferous tubule segments were used to evaluate the number of apoptotic cells. Western blot analyses were performed on cultured seminiferous tubule segments for Bcl-2 family proteins (Bax, Bad, Bcl-w, Bcl-xL) and fas ligand. RESULTS: TNF-alpha promotes cell survival in the rat seminiferous epithelium, and this prosurvival effect can be blocked by infliximab, a TNF-alpha antagonist. Bcl-xL was found to be upregulated in mitochondrial membranes by TNF-alpha, and this upregulation was inhibited by infliximab. Inhibition of NF-kappa B translocation to the nucleus prevented the prosurvival effect of TNF-alpha on seminiferous epithelium. CONCLUSIONS: The present study demonstrates that TNF-alpha promotes cell survival in the rat seminiferous epithelium, and this effect can be blocked by infliximab. This is the first study to show the effects of infliximab in the testis. The prosurvival effect of TNF-alpha might be at least partly mediated by modulating the expression and subcellular localization of Bcl-2 family proteins.

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