227 DIFFERENTIAL REACTIONS OF HUMAN BLADDER SMOOTH MUSCLE CELLS TO HYPOXIA AND OXIDATIVE STRESS

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology1 Apr 2011227 DIFFERENTIAL REACTIONS OF HUMAN BLADDER SMOOTH MUSCLE CELLS TO HYPOXIA AND OXIDATIVE STRESS Kazem Azadzoi, Subarrao Yalla, and Mike Siroky Kazem AzadzoiKazem Azadzoi Boston, MA More articles by this author , Subarrao YallaSubarrao Yalla Boston, MA More articles by this author , and Mike SirokyMike Siroky Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.337AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent clinical studies have suggested a close correlation between decreased pelvic blood flow and lower urinary tract symptoms (LUTS) in elderly patients. LUTS improvement with alpha-adrenocepor blockers was associated with increased bladder and prostate blood flow. Studies of experimental models have suggested key roles for hypoxia and oxidative stress in the overactive and obstructed bladders. Our goal was to explore the influence of hypoxia and oxidative stress in human bladder smooth muscle cell injury and ultrastructural aberration. METHODS Confluent cultured human bladder primary smooth muscle cells were incubated under normoxia (21% oxygen, 5 dishes) and continuous hypoxia (2% oxygen, 5 dishes) conditions for 48 hours using a computerized servo-control cell oxycycler system. To study oxidative stress, another five dishes of cells were incubated under cyclical hypoxia/reoxygenation using 2% oxygen for 30 minutes followed by reoxygenation with 21% oxygen for one hour; cycling in this manner for 48 hours. After 48 hours, samples were collected and processed for fluorometric and enzyme immunoassay of cell injury and transmission electron microscopy. RESULTS Lipid peroxidation was found in cells exposed to hypoxia and oxidative stress while protein oxidation was evident in cellular oxidative stress only. The levels of oxidatively modified products increased after cell exposure to oxidative stress while increased nitrosative products were evident in both hypoxic and oxidative stress conditions. Cellular antioxidant capacity decreased in oxidative stress but remained unchanged in hypoxia. Forty-eight hours of hypoxia and oxidative stress had no significant effect on cell senescence. Electron microscopy of cells showed thickened deformed cell membrane, swollen mitochondria and enlarged endoplasmic reticulum (ER) in cells exposed to hypoxia. Distorted partially lost cell membrane with increased caveolae, enlarged mitochondria with degraded or lost cristae, splintered ER, and increased cytoplasmic lysosomes and multivesicular bodies were evident in oxidative stress. CONCLUSIONS Human bladder smooth muscle cells are highly sensitive to hypoxic and oxidative stress conditions exhibiting specific biological and ultrastructural reactions. Bladder smooth muscle cell reactions to hypoxia are consistent with cell survival signaling to cope with lack of oxygen. Changes in oxidative stress correspond to extensive damage, cellular ultrastructural disintegration and deterioration of the subcellular elements. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e92-e93 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazem Azadzoi Boston, MA More articles by this author Subarrao Yalla Boston, MA More articles by this author Mike Siroky Boston, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...