Effects of Nicotine on MPTP-induced Parkinson's Disease Animal Model / 대한해부학회지

Parkinson's disease (PD) is a progressive neurological disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Despite extensive researches, the etiology of this disease is still unknown; however, the prevalence of PD is lower in the population of cigarette smokers. In this study, the effects of nicotine were investigated on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease animal model and the spontaneous locomotor activity was analyzed. In comparison with MPTP-induced PD animals, nicotine-treated PD animals exhibited significant improvement in the number of dopaminergic neurons in the SNpc, the relative density of dopaminergic axon terminals in the striatum, and locomotor activity. Also, MPTP-induced astrogliosis was prevented by nicotine treatment. These results suggest that the dopamine depletion in the SNpc and striatum and the decreased spontaneous locomotor activity were prevented by nicotine treatment in the MPTP-induced PD animal model.

Functional characteristics of neutral amino acid transporter in opossum kidney (OK) cells

The characteristics of Na+/-dependent cycloleucine uptake was investigated in OK cells with regard to substrate specificity and regulation by protein kinase C (PKC). Inhibition studies with different synthetic and natural amino acids showed a broad spectrum affinity to neutral amino acids regardless of their different side chains including branched or aromatic, indicating that the Na+/-dependent cycloleucine uptake in OK cells is mediated by System B-o or System B degree -like transporter rather than the classical System A or ASC. Phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate, but not 4 alpha-PMA elicited a time-dependent biphasic stimulation of Na+/-dependent cycloleucine uptake, which produced early transient peak at 30 min and late sustained peak at 180 min. Both the early and late stimulations by PMA were due to an increase in Vmax and not due to a change in Km. PKC inhibitors blocked both the early and late stimulation by PMA, while protein synthesis inhibitors blocked the late stimulation only. These results suggest the existence and regulation by PKC of System B degree or System B degree -like broad spectrum transport system for neutral amino acids in OK cells.

Cloning of mouse AQP-CD gene

Water transport in highly-permeable membranes is facilitated by some specialized pathways, which are called aquaporins (AQP). AQP1 (AQP-CHIP) is the first recognized aquaporin identified from red cells and renal proximal tubules. Up until now 4 other aquaporin homologs have been reported. Each aquaporin has its unique tissue distribution and regulatory mechanisms. To elucidate molecular mechanisms for their transcription regulation and tissue-specific expression isolation of aquaporin genes is required. To clone promoters of the AQP family mouse genomic library was screened by the 1st exon-specific probe of AQP4, and 5 different plaques were positively hybridized. Phage DNAs were purified and characterized by restriction mapping and sequencing. One of them is the mouse AQP-CD gene. The gene was consisted of 4 exons and the exon-intron boundaries of mouse AQP-CD gene were identified at identical positions in other related genes. The 5'-flanking region of AQP-CD gene contains one classic TATA box, a GATA consensus sequence, an E-box and a cyclic AMP-responsive element. The cloning of the mouse AQP-CD gene, of which product is expressed in the collecting duct and is responsible for antidiuresis by vasopressin, will contribute to understand the molecular mechanisms of tissue-specific expression and regulation of AQP-CD gene under various conditions.