Later the possibilities of preventing the neurotoxicity generated by levodopahave been demonst

Kinds of polyamine excretion proteins, consisting of 12 Nodakenin transmembrane segments, to maintain the optimal concentrations of polyamines. Among them, TPO1 and TPO5 were the most active proteins. Since the polyamine metabolizing enzyme spermidine/spermine N1-acetyltransferase is not present in yeast, this likely explains why five kinds of excretion proteins are present. Furthermore, the existence of putrescine and spermidine transport protein LmPOT1 in Leishmania major, putrescine and cadaverine transport proteins TcPOT1.1 and TcPOT1.2 in Trypanosoma cruzi, the putrescine, spermidine and spermine transporter encoded by the RMV1 gene in Arabidopsis thalianaand carnitine and spermidine transporter SLC22A16 in NT2/D1 human testicular cancer cellshas been reported. It has been also reported that putrescine and agmatine are taken up by human OCT2, and spermidine is by mouse OCT2. In this communication, we studied the properties of putrescine, agmatine and spermidine uptake by hOCT2 in detail, and found that the active center of putrescine, agmatine and spermidine uptake are located on a-helices 9 to 12. Amino acid residues on ahelices 9 to 12 involved in the uptake of the three amines were identified, and modeling of polyamine binding to hOCT2 was carried out based on the identification of functional amino acids. In mammalian cells, spermidine uptake by human carnitine transporter SLC22A16, putrescine and agmatine uptake by hOCT2, spermidine uptake by mouse OCT2, and agmatine uptake by hMATE1have been previously reported. Although agmatine is a diamine like putrescine, it inhibited cell growth by inhibition of ornithine decarboxylase, a rate limiting enzyme of polyamine biosynthesis, through the stimulation of synthesis of antizyme, which is not only an inhibitor of ODC but also accelerates the degradation of ODC ; i.e. agmatine has an anti-polyamine effect on cell growth. Thus, in this study, putrescine, spermidine and agmatine uptake by hOCTs and hMATEs, normally found in the kidney, were systematically studied. These proteins are thought to be expressed in many tissues. Our results confirmed that hOCT2 catalyzes putrescine, agmatine and spermidine uptake. The uptake of putrescine and agmatine by hOCT2 was slightly more efficient than that of spermidine. Agmatine uptake was also catalyzed by hOCT2, hOCT3 and hMATE1. However, no significant amounts of agmatine were detected in any organs of mice, which were fed by normal diet. Only a few kinds of food and drink contain agmatine. Thus, hOCT2 functions as putrescine and spermidine transporter in vivo. Fullerenes and their derivatives are considered perspective for various applications in medicine and pharmacology. Particularly, C60-fullerene and tris-malonic C60-fullereneare known as free radical scavengers, that have been shown to protect cells from free radicalsthat can induce apoptotic injuries in vitroas well as in different cell types: neuronal cells, hepatoma cellsand epithelial cells. At the same time, some of fullerene derivatives inhibit HIV-protease, what gives another prospect for their biomedical use. Harhaji et al. demonstratedthe antitumor effect of the water suspension of C60 on glioma cell cultures when irradiated by light: high concentrations of fullerene caused necrosis, while low concentrations stopped proliferation of the cells and 4-Aminohippuric Acid eventually lead to autophagy. Fumelli et al.have demonstrated that carboxyfullerenes protected human keratinocytes from apoptosis induced by ultraviolet-Birradiation.

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