Extraneural CGRP Induces Oxidative Stress in Kidney Proximal Tubule Epithelial Cells

Abstract

Calcitonin gene-related peptide (CGRP) is the most abundant neuropeptide in primary afferent sensory neurons. Exogenous CGRP can induce cell death in kidney tubular cells. The objective of this study was to determine whether exogenous CGRP could induce reactive oxygen species (ROS) production in kidney proximal tubule epithelial cells and whether CGRP-induced ROS production might contribute to cell death. In HK-2, LLCPK1 and TCMK-1 cell lines derived from human, pig, and mouse respectively, administration of CGRP increased cell death in timeand dose-dependent manners, as demonstrated by decreased cell viability. Exogenous CGRP also increased ROS production levels in those cell lines. Treatment with CGRP receptor antagonist (CGRP) significantly inhibited the increases in cell death and ROS production in CGRP-exposed cells. Furthermore, treatment with a ROS scavenger (MnTMPyP) markedly reduced kidney proximal tubule epithelial cell death after CGRP administration. Taken together, these data suggest that extraneural CGRP can induce cell death through excessive oxidative stress in kidney proximal tubule epithelial cells.