Hydrogen Peroxide Stimulates Exosomal Cathepsin B Regulation of the Receptor for Advanced Glycation End‐Products (RAGE) |
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| Authors: | Charles A Downs Viet D Dang Nicholle M Johnson Nancy D Denslow Abdel A Alli |
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| Institution: | 1. College of Nursing, Biobehavioral Healthscience Division & College of Medicine, Department of Medicine Division of Translational & Regenerative Medicine, The University of Arizona, Tucson, Arizona;2. Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida;3. Department of Physiology and Functional Genomics and Department of Medicine Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida |
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| Abstract: | Exosomes are nano‐sized vesicles that are secreted into the extracellular environment. These vesicles contain various biological effector molecules that can regulate intracellular signaling pathways in recipient cells. The aim of this study was to examine a correlation between exosomal cathepsin B activity and the receptor for advanced glycation end‐products (RAGE). Type 1 alveolar epithelial (R3/1) cells were treated with or without hydrogen peroxide and exosomes isolated from the cell conditioned media were characterized by NanoSight analysis. Lipidomic and proteomic analysis showed exosomes released from R3/1 cells exposed to oxidative stress induced by hydrogen peroxide or vehicle differ in their lipid and protein content, respectively. Cathepsin B activity was detected in exosomes isolated from hydrogen peroxide treated cells. The mRNA and protein expression of RAGE increased in cultured R3/1 cells treated with exosomes containing active cathepsin B while depletion of exosomal cathepsin B attenuated RAGE mRNA and protein expression. These results suggest exosomal cathepsin B regulates RAGE in type 1 alveolar cells under conditions of oxidative stress. J. Cell. Biochem. 119: 599–606, 2018. © 2017 Wiley Periodicals, Inc. |
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| Keywords: | EXOSOMES LIPIDOMICS PROTEOMICS |
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