Wang Yangyang, Suominen Janne S, Parvinen Martti, Rivero-Muller Adolfo, Kiiveri Sanne, Heikinheimo Markku, Robbins Ian, Toppari Jorma
Department of Physiology and Pediatrics, University of Turku, Kiinamyllynkatu 10, Turku 20520, Finland.
Mol Cell Endocrinol. 2005 Dec 21;245(1-2):111-20. doi: 10.1016/j.mce.2005.11.004. Epub 2005 Dec 15.
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.
凋亡抑制蛋白c-IAP1和c-IAP2在大鼠睾丸中高表达,并可能在睾丸细胞凋亡中发挥调节作用。为了更好地了解它们在精子发生过程中的功能,我们分析了它们在大鼠睾丸中的时空分布、旁分泌干细胞因子(SCF)如何控制它们的表达以及它们如何影响Fas介导的细胞凋亡。在整个生精上皮周期中,c-IAP1和c-IAP2均呈现转录表达周期。c-IAP1蛋白在B型精原细胞、前细线期、细线期和偶线期精母细胞中呈弥漫性核分布。在粗线期精母细胞中,c-IAP1与SUMO-1在XY小体中共定位。从粗线期VI阶段开始,c-IAP2蛋白在精母细胞、圆形精子细胞、伸长精子细胞和睾丸间质细胞中呈细胞质分布。其表达受SCF上调。抑制IAP活性导致生殖细胞对Fas介导的细胞凋亡更敏感。这些结果表明IAPs在生精细胞凋亡调节中起重要作用。