Methods: Tubular epithelial cell line NRK cells were exposed to nephrotoxic agents. The generation of ROS was detected by using a Total ROS/Superoxide Detection Kit. Cell viability was evaluated by cell shape change, calcein/ propidium iodide staining, cleavage of caspase 3 and WST

assay. The expression, selleck inhibitor function and role of GJs were evaluated through scrape-loading dye transfer, Western blot analysis and modulation of gap junctions with chemical and genetic approaches. Results: 1) Exposure of renal tubular cells to aminoglycosides caused the loss of cellular viability, which was preceded by an elevated level of ROS generation, connexin43 (Cx43) phosphorylation and gap junctional intercellular communication. 2) The cell injury induced by aminoglycosides was significantly attenuated by antioxidant GSH and NAC.

The protective action of these antioxidants was associated with a reduced level of gap junction protein Cx43. 3) Dysfunction of gap junctions with chemical inhibitors or downregulation of Cx43 with siRNA protected the cells from aminoglycoside-induced cell injury. 4) Treatment of cells with GJ inhibitors or Cx43 siRNA resulted in an increased phosphorylation of Akt. Inhibition of AKT exaggerated aminoglycoside-induced tubular cell injury and abolished the protective effect of GJ inhibitors. Conclusion: We characterized GJs as a presently unrecognized factor controlling renal tubular cell susceptibility to nephrotoxic drugs, possibly through modulation of cellular response to oxidative stress. Modulation of GJs could Cobimetinib mouse be developed as a novel therapeutic approach for prevention and treatment of drug-induced renal tubular cell injury. Nabilone HWANG SEON DEOK, YU JI HYUN, CHUNG BYUNG HA, YANG CHUL WOO, KIM YONG-SOO, PARK CHEOL WHEE, CHOI BUM SOON Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea Introduction: Aging is a multifactorial process characterized

by a progressive decline in physiological function. Decreased kidney function is associated with cardiovascular disease and mortality. Therefore, increasing our insight into kidney aging by understanding the anatomic, physiologic, and pathologic changes of aging in the kidney is important to prevent disastrous outcomes in elderly people. Methods: Male 2-, 12-, and 24-month-old C57/BL6 mice were used in this study. We measured histological change, oxidative stress, aging-related protein expression in the kidneys. Results: Twenty-four-month-old mice displayed increased albuminuria. Creatinine clearance decreased with aging, although this was not statistically significant. There were increases in mesangial volume and tubulointerstitial fibrosis in 24-month-old mice. There were also increases in F4/80 expression groups (0.11 ± 0.06% vs. 0.4 ± 0.11%, 2.5 ± 0.52%; **p < 0.01 vs. 2 M) and in apoptosis detected by TUNEL (p < 0.01 vs. 2 M) assay. Urine isoprostane (7.4 ± 0.3% vs. 19.4 ± 0.78%, 21.9 ± 1.9%; *p < 0.05 vs. 2 M, **p < 0.01 vs.