MP49-12 EFFECT OF BCG EXPOSURE ON ENZYMATIC REGULATORS OF CELLULAR OXIDATIVE STRESS IN UROTHELIAL CARCINOMA CELLS (2015)

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 2015MP49-12 EFFECT OF BCG EXPOSURE ON ENZYMATIC REGULATORS OF CELLULAR OXIDATIVE STRESS IN UROTHELIAL CARCINOMA CELLS Gopitkumar Shah, Fanghong Chen, Guangjian Zhang, Balaraman Kalyanaraman, and William See Gopitkumar ShahGopitkumar Shah More articles by this author , Fanghong ChenFanghong Chen More articles by this author , Guangjian ZhangGuangjian Zhang More articles by this author , Balaraman KalyanaramanBalaraman Kalyanaraman More articles by this author , and William SeeWilliam See More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.516AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prior work has demonstrated that exposure of urothelial carcinoma (UC) cells to Bacille Calmette Guerin (BCG) alters cellular redox status. Recent findings that BCG generates H2O2, and that H2O2 production by BCG is required for the UC cell response, provides the probable mechanistic link of BCG to cellular oxidative stress (COS) generation. Eukaryotic cells possess multiple enzymatic pathways which function to mitigate oxidative stress and thereby minimize COS associated cellular damage. To date, effect of BCG on these regulators of COS have not been defined. The objective of the study is to assess role of BCG, BCG viability and H2O2 on antioxidant enzyme levels in human UC cell lines. METHODS Two human UC cell lines 253J and T24 were used in the study. Activities of antioxidants enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) was measured at different time points post BCG/heat killed BCG exposure. Inhibition of BCG internalization and pharmacologic scavenging of H2O2 was studied for their effect on antioxidant enzyme levels. RESULTS BCG exposure induced time dependent changes in enzymes levels for all three of the COS regulators studied. SOD activity was significantly increased at 6h but did not show any change at 12h and 24h (p ≤ 0.05, T24; p ≤ 0.01, 253J). GPx activity showed significant increase at 6h (p ≤ 0.05, T24, 253J) but showed slight decrease at 12h (p = 0.12) and 24h (p = 0.2). Catalase activity did not show any increase at 6h (p = 0.4, T24; p = 0.5, 253J), but showed significant increase at 12h and 24h (p ≤ 0.01, T24, 253J). Loss of BCG viability (associated with decreased H2O2 production) resulted in significantly reduced activation of SOD (p ≤ 0.05) catalase (p ≤ 0.001) and GPx (p ≤ 0.01) compared to viable BCG. Inhibition of BCG internalization and pharmacological scavenging of H2O2 nullified BCG mediated induction of antioxidant enzymes. CONCLUSIONS BCG generates COS in UC cells in a BCG-viability dependent manner. In order to limit the magnitude of COS associated with BCG exposure, the UC cell machinery up regulates antioxidant enzymes including SOD, catalase and GPx. H2O2 appears to be the major contributor for the UC cell response to COS as pretreatment with H2O2 scavenger nullifies the induction of antioxidants machinery. Agents which impact the ability of the UC cell to respond to COS have the potential to increase or decrease BCG induced cellular injury. Targeting cellular antioxidant enzymes represents an attractive strategy for improving BCG treatment efficacy. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e607 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gopitkumar Shah More articles by this author Fanghong Chen More articles by this author Guangjian Zhang More articles by this author Balaraman Kalyanaraman More articles by this author William See More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...