title: Involvement of mitogen-activated protein kinases (MAPKs) during testicular ischemia-reperfusion injury in nuclear factor-kappaB knock-out mice.
abstract: Nuclear factor kappa-B (NF-kappaB), extracellular regulated kinase (ERK 1/2) and c-jun-N terminal kinase (JNK) play an important role in testicular ischemia. We investigated the patterns of ERK1/2, JNK and p38 activation in NF-kappaB knockout (KO) mice subjected to testicular torsion. KO and normal littermate wild-type (WT) animals underwent at 1 h testicular ischemia followed by 24 h reperfusion (TI/R). Sham testicular ischemia-reperfusion mice served as controls. ERK 1/2, JNK and p38 expression by western blot analysis, tumor necrosis factor-alpha (TNF-alpha) expression (RT-PCR and western blot analysis) and a complete histological examination were carried out. TI/R caused a greater increase in phosphorylated form of ERK 1/2 in KO mice than in WT animals in either the ischemic testis and the contralateral one. By contrary, active form of JNK and p38 were completely abrogated in both testes of KO mice, while WT animals showed a significant activation of those kinases in both testes. TNF-alpha expression was markedly reduced in KO mice when compared to WT mice either at the mRNA and the protein level. Finally TI/R-induced histological damage was markedly reduced in KO mice. Our data indicate that NF-kappaB plays a pivotal role in the development of testicular ischemia-reperfusion injury and suggest that, in the absence of the transcriptional factor, the up-stream signal JNK and p38 may be abrogated while ERK 1/2 activity is enhanced.
authors.affiliation: Department of Experimental and Clinical Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy.
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Pietro
authors.initials: P
authors.lastname: Antonuccio
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fiumara
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Piero Antonio
authors.initials: PA
authors.lastname: Nicotina
authors.forename: Salvatore
authors.initials: S
authors.lastname: Arena
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Carmelo
authors.initials: C
authors.lastname: Romeo
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003593:Cytoplasm / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015427:Reperfusion Injury; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000098:blood supply* / Q000201:enzymology
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D011494:Protein Kinases; D020928:Mitogen-Activated Protein Kinases