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Activation of the nuclear factor kappa B pathway following ischemia-reperfusion of the murine testis.
J Androl. 2005 Jan-Feb; 26(1):129-35.JA

Abstract

Ischemia-reperfusion (IR) of the testis results in testicular oxidative stress and germ cell-specific apoptosis. Nuclear factor kappa B (NF-kappaB) is a nuclear transcription factor involved in the control of a number of cellular processes, and its activation is part of the cellular stress response to a variety of factors including cytokine stimulation, irradiation, and IR. The present study investigates NF-kappaB activation after IR of the murine testis and potential downstream target genes of that activation. Mice were subjected to a period of testicular ischemia followed by 0-4 hours of reperfusion. Activation of NF-kappaB was assessed by 1) Western blot analysis of the NF-kappaB inhibitory protein, IkappaBalpha; 2) immunohistochemistry for IkappaBalpha; and 3) TranSignal NF-kappaB target gene array (107 genes) analysis. Results demonstrate that IkappaBalpha is phosphorylated on serine 32 reaching a peak by 2 hours after IR of the testis. A decrease in total IkappaBalpha was also noted at 2 hours after IR, consistent with the rapid degradation of the phosphorylated protein. Phosphorylation and degradation of IkappaBalpha is indicative of NF-kappaB activation. Immunolocalization revealed IkappaBalpha specifically in Sertoli cells of the murine testis. Results of the TranSignal target gene array revealed that the expression of 9 genes was consistently changed 2 hours after IR of the testis, 3 of which increased in expression and 6 of which were down-regulated. Most notably, high-mobility group nucleosomal binding domain 1 increased in expression while platelet-derived growth factor B and Wilms tumor homolog decreased. These results suggest that testicular IR releases the suppression of NF-kappaB by IkappaBalpha in Sertoli cells. Activation of the NF-kappaB pathway in the testis resulted in an alteration of expression of potential NF-kappaB target genes, some increased while others decreased. The specific roles of these genes in the testicular response to IR remains to be determined.

Authors+Show Affiliations

Department of Urology Box 800422, University of Virginia Health System, Charlottesville, VA 22908, USA. jl6n@virginia.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15611577

Citation

Lysiak, Jeffrey J., et al. "Activation of the Nuclear Factor Kappa B Pathway Following Ischemia-reperfusion of the Murine Testis." Journal of Andrology, vol. 26, no. 1, 2005, pp. 129-35.
Lysiak JJ, Bang HJ, Nguyen QA, et al. Activation of the nuclear factor kappa B pathway following ischemia-reperfusion of the murine testis. J Androl. 2005;26(1):129-35.
Lysiak, J. J., Bang, H. J., Nguyen, Q. A., & Turner, T. T. (2005). Activation of the nuclear factor kappa B pathway following ischemia-reperfusion of the murine testis. Journal of Andrology, 26(1), 129-35.
Lysiak JJ, et al. Activation of the Nuclear Factor Kappa B Pathway Following Ischemia-reperfusion of the Murine Testis. J Androl. 2005 Jan-Feb;26(1):129-35. PubMed PMID: 15611577.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of the nuclear factor kappa B pathway following ischemia-reperfusion of the murine testis. AU - Lysiak,Jeffrey J, AU - Bang,Hyun J, AU - Nguyen,Quoc An T, AU - Turner,Terry T, PY - 2004/12/22/pubmed PY - 2005/4/14/medline PY - 2004/12/22/entrez SP - 129 EP - 35 JF - Journal of andrology JO - J Androl VL - 26 IS - 1 N2 - Ischemia-reperfusion (IR) of the testis results in testicular oxidative stress and germ cell-specific apoptosis. Nuclear factor kappa B (NF-kappaB) is a nuclear transcription factor involved in the control of a number of cellular processes, and its activation is part of the cellular stress response to a variety of factors including cytokine stimulation, irradiation, and IR. The present study investigates NF-kappaB activation after IR of the murine testis and potential downstream target genes of that activation. Mice were subjected to a period of testicular ischemia followed by 0-4 hours of reperfusion. Activation of NF-kappaB was assessed by 1) Western blot analysis of the NF-kappaB inhibitory protein, IkappaBalpha; 2) immunohistochemistry for IkappaBalpha; and 3) TranSignal NF-kappaB target gene array (107 genes) analysis. Results demonstrate that IkappaBalpha is phosphorylated on serine 32 reaching a peak by 2 hours after IR of the testis. A decrease in total IkappaBalpha was also noted at 2 hours after IR, consistent with the rapid degradation of the phosphorylated protein. Phosphorylation and degradation of IkappaBalpha is indicative of NF-kappaB activation. Immunolocalization revealed IkappaBalpha specifically in Sertoli cells of the murine testis. Results of the TranSignal target gene array revealed that the expression of 9 genes was consistently changed 2 hours after IR of the testis, 3 of which increased in expression and 6 of which were down-regulated. Most notably, high-mobility group nucleosomal binding domain 1 increased in expression while platelet-derived growth factor B and Wilms tumor homolog decreased. These results suggest that testicular IR releases the suppression of NF-kappaB by IkappaBalpha in Sertoli cells. Activation of the NF-kappaB pathway in the testis resulted in an alteration of expression of potential NF-kappaB target genes, some increased while others decreased. The specific roles of these genes in the testicular response to IR remains to be determined. SN - 0196-3635 UR - https://www.unboundmedicine.com/medline/citation/15611577/Activation_of_the_nuclear_factor_kappa_B_pathway_following_ischemia_reperfusion_of_the_murine_testis_ DB - PRIME DP - Unbound Medicine ER -