title: Characterization of urocortin as an anti-apoptotic protein in experimental ischemia-reperfusion model of the rat testis.
abstract: The objective of this study was to investigate the role of urocortin in testicular apoptosis using an experimental ischemia-reperfusion rat model. To evaluate the change in urocortin expression and apoptotic status in the testes following ischemia-reperfusion, the left testes of rats were rotated clockwise by 720° for 1 h, and were then harvested at 0, 1, 3, 6 and 24 h after detorsion (n = 5 in each group). A time-dependent increase in the expression levels of urocortin was noted until 6 h after reperfusion, but the expression of urocortin was markedly decreased 24 h after reperfusion. However, a TUNEL assay showed that the proportion of germ cells undergoing apoptosis significantly increased 24 h after reperfusion compared with that of 6 h after reperfusion. To clarify whether or not urocortin directly regulates the testicular apoptosis induced by ischemia-reperfusion, either astressin, an antagonist of urocortin, or normal saline was injected into the rat testes 15 min before detorsion, followed by the testicular torsion. The testes were then removed 3 h after detorsion (n = 5 in each group). The testicular injection of astressin significantly increased the proportion of TUNEL-positive germ cells, and significantly decreased expression of Bcl-2 and Bcl-xL. In addition, the level of phosphorylated ERK 1/2, but not that of phosphorylated Akt, was significantly reduced by the intratesticular administration of astressin. These findings suggest that urocortin may play a cytoprotective role in the germ cells in response to ischemia-reperfusion injury through the activation of major anti-apoptotic proteins, as well as by the mitogen-activated protein kinase signaling pathway activation.
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Electronic address: ksumii@med.kobe-u.ac.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Sumii
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Enatsu
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D020869:Gene Expression Profiling; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013086:Spermatic Cord Torsion; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D054832:Urocortins / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494813:Bcl2l1 protein, rat; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C000607145:Ucn protein, rat; D054832:Urocortins; D051020:bcl-X Protein; C104416:astressin; D003346:Corticotropin-Releasing Hormone
keywords: Apoptosis; Ischemia-reperfusion; Male infertility; Testicular torsion; Urocortin