Overexpression of p75NTR in Human Seminoma: A New Biomarker?

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs.

Effect of nerve growth factor dimeric mimetic GK-2 on microcirculation in skeletal muscle on the hind limb ischemia model in rats

The purpose of the study. In experiments on a hind limb ischemia model in rats, the effect of the TrkA-receptor agonist of the NGF 4th loop dimeric dipeptide mimetic compound GK-2 has been studied on microcirculation in ischemic skeletal muscle.Methods. the Hind limb ischemia was caused in white male mongrel rats by the femoral artery resection. The compound GK-2 was administered intravenously (1 mg/kg/day during 14 days). Microcirculation parameters were recorded using a computer laser analyzer "LAKK-OP2". Registration was carried out simultaneously in the intact and operated limb before the operation, 1 and 14 days after it.Results. In the conditions of the hind limb ischemia model, it was shown that the compound GK-2 almost completely restored the perfusion index and its variation coefficient in the ischemic muscle to the intact contralateral limb level by the 14th day after surgery.Conclusion. It can be assumed that the anti-ischemic effect of the compound GK-2 is associated with the restoration of microcirculation as a result of increased neoangiogenesis.

Copper Binding Features of Tropomyosin-Receptor-Kinase-A Fragment: Clue for Neurotrophic Factors and Metals Link

The nerve growth factor (NGF) is a neurotrophin essential for the development and maintenance of neurons, whose activity is influenced by copper ions. The NGF protein exerts its action by binding to its specific receptor, TrkA. In this study, a specific domain of the TrkA receptor, region 58–64, was synthesized and its copper(II) complexes characterized by means of potentiometric and spectroscopic studies. The two vicinal histidine residues provide excellent metal anchoring sites and, at physiological pH, a complex with the involvement of the peptide backbone amide nitrogen is the predominant species. The TrkA peptide is competitive for metal binding with analogous peptides due to the N-terminal domain of NGF. These data provide cues for future exploration of the effect of metal ions on the activity of the NGF and its specific cellular receptor.