title: Role of p97/Valosin-containing protein (VCP) and Jab1/CSN5 in testicular ischaemia-reperfusion injury.
abstract: The most significant complication of testicular ischaemia is loss of the testis, which may lead to infertility. Testicular ischaemia damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated protein aggregates. Despite recent advances, the factors leading to impairment of spermatogenesis owing to testicular ischaemia remain poorly understood. This study was undertaken to gain insight into the cellular and molecular mechanism underlying torsion induced germ cell apoptosis. Male rats were subjected to 2 h torsion, and testes were examined at 2, 4, 12 and 24 h after torsion repair (reperfusion). Ischaemia-reperfusion (IR) of the testes resulted in apoptosis which was revealed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) technique. At 12 h after torsion repair germ cell loss reached peak, then decreased at 24 h repair. Western blotting showed that apoptotic proteins (active caspase 3, caspase 9 and Bax) gradually was upregulated at 12 h reperfusion, however anti-apoptotic protein (Bcl2) was downregulated in the relevant IR treatment. Furthermore, Jab1/CSN5 expression was gradually upregulated and p97/VCP expression was downregulated in IR injury according to western blotting and immunohistochemistry. To test further whether polyubiquitination was also involved in IR injury, the expression of polyubiquitinated proteins was examined, which showed that polyubiquitinated proteins were significantly increased in IR injury. These finding suggest that p97/VCP and Jab1/CSN5 provide a novel signaling pathway for testicular ischaemia and may play an important role in IR injury induced cell death in rat testis.
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey. sevilcayli@yahoo.com.
authors.forename: Sevil
authors.initials: S
authors.lastname: Cayli
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Ocakli
authors.affiliation: Department of Pediatric Surgery, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Senel
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Kafkas University, Kars, Turkey.
authors.forename: Nilnur
authors.initials: N
authors.lastname: Eyerci
authors.affiliation: Department of Endocrinology and Metabolism, Diskapi Teaching and Research Hospital, Ankara, Turkey.|Department of Internal Medicine, School of Medicine (Kastamonu), Hacettepe University, Ankara, Turkey.
authors.forename: Tuncay
authors.initials: T
authors.lastname: Delibasi
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D000075686:COP9 Signalosome Complex; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012399:Rotation; D015398:Signal Transduction; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D054875:Ubiquitination; D000074405:Valosin Containing Protein; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D018797:Cell Cycle Proteins; C490121:Gps1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000075686:COP9 Signalosome Complex; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein; C000614180:Vcp protein, rat
keywords: Cell death; Ischaemia–reperfusion injury; Jab1/CSN5; Rat; Testis; p97/VCP