Significance of downregulation of renal organic cation transporter (SLC47A1) in cisplatin-induced proximal tubular injury.

BACKGROUND/AIM: To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs) influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1) in tubular cells. MATERIALS AND METHODS: To detect changing expression of MATE1/SLC47A1 in dose- and time-dependent manners, human proximal tubular epithelial cells were incubated with AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human proximal tubular epithelial cells were incubated with cisplatin or carboplatin. RESULTS: On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased in tubular cells. In addition, the toxicities of cisplatin were increased in tubular cells that had been pretreated with AGEs. However, the toxicities of carboplatin were smaller than that of cisplatin in proximal tubular epithelial cells. CONCLUSION: The expression of the MATE1/SLC47A1 is decreased by AGEs, which increases the risk for proximal tubular injury.

Electronic structure of brain: structure-activity relationships between electronic structure and neurotransmitters based on molecular hardness concept.

In order to understand the relation between the electronic structure of neurotransmitters and the brain, a model of the brain based on absolute hardness (eta) and absolute electronegativity (chi) is described. It was found that the coordinate r(chi, eta) of electronic structures of neurotransmitters obtained using the parameters eta and chi can be graphically classified into three groups: catecholamine type (group I), gamma-aminobutanoic acid (GABA) type (group II), and acetylcholine (ACh) type (group III) in the eta-chi diagram. The results suggest that the brainstem and neocortex in the brain are chemically soft and hard, respectively, because they show that the myelinated nerve is chemically soft and the unmyelinated nerve is chemically hard. If one calculates the r(chi, eta) to understand which group a drug belongs to, one can predict the target receptors of the drug from the eta-chi diagram. Using eta-chi maps, one is then able to design medications like antidepressants, tranquilizers, and ACh agonists.