Role of p97/Valosin-containing protein (VCP) and Jab1/CSN5 in testicular ischaemia-reperfusion injury


ÇAYLI S. , OCAKLI S., Senel U., EYERCİ N., Delibasi T.

JOURNAL OF MOLECULAR HISTOLOGY, cilt.47, sa.1, ss.91-100, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 47 Konu: 1
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1007/s10735-016-9652-9
  • Dergi Adı: JOURNAL OF MOLECULAR HISTOLOGY
  • Sayfa Sayıları: ss.91-100

Özet

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.