AMPK Potentiates Hypertonicity-induced Apoptosis by Suppressing NFκB/COX-2 in Medullary Interstitial Cells

• DOI: 10.1681/asn.2010080822
• Publication Date: 2011-09-10T02:51:19Z
• Authors: Qifei Han; Xiaoyan Zhang; Rui Xue; Hang Yang; Yunfeng Zhou; Xiaomu Kong; Pan Zhao; Jing Li; Jichun Yang; Yi Zhu; Youfei Guan
• Keywords: AMP-Activated Protein Kinase; Renal medulla

Cells residing in the hypertonic, hypoxic renal medulla depend on dynamic adaptation mechanisms to respond changes energy supply and demand. The serine/threonine kinase 5'-AMP protein (AMPK) is a sensor of cellular status, but whether it contributes survival cells unknown. Here, hypertonic conditions induced decrease AMPK phosphorylation within 12 hours medullary interstitial (RMIC), followed by gradual return baseline levels. Activation markedly increased hypertonicity-induced apoptosis RMICs suppressed both NFκB nuclear translocation cyclooxygenase-2 (COX-2) activation; overexpression COX-2 significantly attenuated these effects. activation also reduced generation reactive oxygen species expression tonicity-responsive enhancer-binding protein, which prevented upregulation osmoprotective genes. In vivo, pharmacologic led massive dysfunction setting water deprivation mice. Taken together, results identify critical role for maintenance RMIC viability suggest that modulates NFκB-COX-2 pathway medulla. Furthermore, this study raises safety concerns development activators as anti-diabetic drugs, especially patients prone dehydration.