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Deficiency in tuberin resulted in increased oxidative <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage in renal cells. In this study, the role of tuberin in the regulating of <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> oxidases was investigated. Formation of <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> and activity of <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> oxidases were significantly higher in mouse embryonic fibroblasts and in primary culture of rat renal proximal tubular epithelial tuberin\u2010deficient cells compared to wild\u2010type cells. In addition, expression of <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> oxidase (Nox)1, Nox2, and Nox4 (Nox isoforms) was higher in mouse embryonic fibroblasts and renal proximal tubular epithelial tuberin\u2010deficient cells compared to wild\u2010type cells. Furthermore, activity levels of <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> oxidases and protein expression of all Nox isoforms were higher in the renal cortex of rat deficient in tuberin. However, treatment of tuberin\u2010deficient cells with rapamycin showed significant decrease in protein expression of all Nox. Significant increase in protein kinase C \u03b2<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> expression was detected in tuberin\u2010deficient cells, whereas inhibition of protein kinase C \u03b2<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> by bisindolylmaleimide I resulted in decreased protein expression of all Nox isoforms. In addition, treatment of mice deficient in tuberin with rapamycin resulted in significant decrease in all Nox protein expression. Moreover, protein and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression of all Nox were highly expressed in tumor kidney tissue of patients with tuberous sclerosis complex compared to control kidney tissue of normal subjects. These data provide the first evidence that tuberin plays a novel role in regulating <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> generation, <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> oxidase activity, and Nox expression that may potentially be involved in development of kidney tumor in patients with tuberous sclerosis complex.<\/jats:p>","DOI":"10.1111\/cas.12984","type":"journal-article","created":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T10:14:31Z","timestamp":1465467271000},"page":"1092-1100","source":"Crossref","is-referenced-by-count":10,"title":["Tuberin regulates reactive oxygen species in renal proximal cells, kidney from rodents, and kidney from patients with tuberous sclerosis complex"],"prefix":"10.1111","volume":"107","author":[{"given":"Samy L.","family":"Habib","sequence":"first","affiliation":[{"name":"Geriatric Research Education and Clinical Department South Texas Veterans Health Care System San Antonio 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