Mouse anti-Human CREM monoclonal antibody, clone 4C6

Background/Aims: Transcription factors coupled to cyclic adenosine mono phosphate (cAMP) signalling in the cAMP-responsive elements binding (CREB)/ATF family constitute a family of activators or repressors that bind to cAMP-responsive promoter elements (CREs) in the regulatory regions of cAMP-inducible genes. A role for CREB/ATF family has been advocated in the control of hepatocellular carcinoma progression. CREB appears to be activated by the X protein of hepatitis B virus, which links to the unphosphorylated form of CREB and activates transcription, thus obviating an otherwise indispensable Ser-133 phosphorylation. Identification of factors capable of triggering transcription via cAMP-responsive elements modulator (CREM)/CREB signalling in the absence of Ser phosphorylation will improve our knowledge of the molecular mechanism of liver cell proliferation. Methods: To isolate and study proteins binding and activating CREB and/or CREM in the liver, we performed the screening of a mouse liver cDNA library using the Two-Hybrid System. Results: We report the identification and characterization of a novel peptide, VTIP-peptide (VTIP-P), which binds and enhances the activation of CREM/CREB, obviating the need for transcription factor phosphorylation. We demonstrated that VTIP-P physically interacts with the activation domain (AD) of the transcription factors CREB/CREM and activates transcription by modifying their phosphorylation pattern in hepatoma cells. The data allowed the conclusion that VTIP-P binds the AD of CREB and CREM by stabilizing their phosphorylation. Conclusion: The characterization of molecules capable of interfering in the liver with an important pathway such as CREB could be significant in designing and/or developing new therapeutic approaches to the control of liver cell proliferation.

Ethnopharmacological relevance: The pathophysiology of testicular torsion-detorsion is ischemia-reperfusion injury of the testis. In the course of testicular ischemia and reperfusion, over-generation of reactive oxygen species is a major initiating component of the testicular spermatogenic injury. Reactive oxygen species regulate many genes whose expression affects cell-cycle regulation, cell proliferation, and apoptosis. The transcription factor cAMP-responsive element modulator-tau (CREM tau) plays an essential role in spermatogenesis. Psoralea corylifolia, a medicinal herb with anti-oxidative activity, has been used to treat male reproductive dysfunction in traditional Chinese medicine. In this study, we investigated the effect of Psoralea corylifolia on testicular torsion/detorsion-induced injury. Materials and methods: Sixty adult male Sprague-Dawley rats were randomly divided into 3 groups, each containing 20 rats. Rats in the control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720 for 2 h. Rats in the treatment group received the same surgical procedure as the torsion-detorsion group, but Psoralea corylifolia was administered orally. Bilateral orchiectomy was performed on half of the rats in each experimental group at 4 h after detorsion for measurement of malondialdehyde which is an indicator of intratesticular reactive oxygen species content. Orchiectomy was performed on the remaining rats at 3 months after detorsion for analysis of testicular CREM tau expression and spermatogenesis. Results: Unilateral testicular torsion-detorsion caused a significant increase in malondialdehyde level and caused significant decreases in CREM tau expression and spermatogenesis in ipsilateral testes. Psoralea corylifolia treatment significantly decreased malondialdehyde level and significantly increased CREM tau expression and spermatogenesis in ipsilateral testes, compared with torsion-detorsion group. Conclusions: These results suggest that Psoralea corylifolia may protect testicular spermatogenesis by enhancing CREM tau expression by scavenging reactive oxygen species. (C) 2011 Elsevier Ireland Ltd. All rights reserved.