1. c-Jun N-terminal Kinase Supports Autophagy in Testicular Ischemia but Triggers Apoptosis in Ischemia-Reperfusion Injury.
- Author
-
Alotaibi SR, Renno WM, and Al-Maghrebi M
- Subjects
- Male, Animals, Rats, Oxidative Stress, Anthracenes pharmacology, Ischemia metabolism, Ischemia pathology, Spermatic Cord Torsion metabolism, Spermatic Cord Torsion pathology, Spermatogenesis drug effects, Beclin-1 metabolism, Disease Models, Animal, Autophagy, Reperfusion Injury metabolism, Reperfusion Injury pathology, Apoptosis, JNK Mitogen-Activated Protein Kinases metabolism, Testis metabolism, Testis pathology, Rats, Sprague-Dawley
- Abstract
Oxidative stress triggered by testicular torsion and detorsion in young males could negatively impact future fertility. Using a rat animal model for testicular IRI (tIRI), we aim to study the induction of autophagy (ATG) during testicular ischemia and tIRI and the role of oxidative-stress-induced c-Jun N-terminal Kinase (JNK) as a cytoprotective mechanism. Sixty male Sprague-Dawley rats were divided into five groups: sham, ischemia only, ischemia+SP600125 (a JNK inhibitor), tIRI only, and tIRI+SP600125. The tIRI rats underwent an ischemic injury for 1 h followed by 4 h of reperfusion, while ischemic rats were subjected to 1 h of ischemia only without reperfusion. Testicular-ischemia-induced Beclin 1 and LC3B expression was associated with decreased p62/SQSTM1 expression, increased ATP and alkaline phosphatase (AP) activity, and slightly impaired spermatogenesis. SP600125 treatment improved p62 expression and reduced the levels of Beclin 1 and LC3B but did not affect ATP or AP levels. The tIRI-induced apoptosis lowered the expression of the three ATG proteins and AP activity, activated caspase 3, and caused spermatogenic arrest. SP600125-inhibited JNK during tIRI restored sham levels to all investigated parameters. This study emphasizes the regulatory role of JNK in balancing autophagy and apoptosis during testicular oxidative injuries.
- Published
- 2024
- Full Text
- View/download PDF