S involved, on the basis of the observation that strain-induced changes were inhibited by diphenylene

S involved, on the basis of the observation that strain-induced changes were inhibited by diphenylene iodonium (DPI) [26,27]. However, the flavoprotein inhibitor DPI also blocks virtually all cellular oxidase systems, including mitochondrial complex I, nitric oxide (NO) synthase, and xanthine oxidase [28]. Therefore, the inhibition by DPI is not specific for NAD(P)H oxidases. ARA290 cost Furthermore, NAD(P)H oxidaseEb se leEb se leEb sEb sn((n)+E2 (3 .EEEpmol)l)l)Page 5 of(page number not for citation purposes)BMC Cardiovascular Disorders 2006, 6:http://www.biomedcentral.com/1471-2261/6/200 180 160 140 120 100 80 60 40 20# #** ** **in the development of vascular lesions which is highly relevant to the cardiovascular health of individuals susceptible to harm from elevated estrogen exposure. Findings of this study may further expand research defining the underlying mechanism of how estrogen may promote vascular lesions. It PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25112874 also provides important information for the design of new antioxidant-based drugs or new antioxidant gene therapy to protect the cardiovascular health of individuals sensitive to estrogen.DNA Synthesis( of control)7p mo l)mo l)CT RL7f mool)fm o7p mpmol)l)l)E2 (36 7fE2 (3(3 .(3 .E(3.AbbreviationsROS, reactive oxygen species; E2, 17-estradiol; ER, estrogen receptor; HUVECs, Human umbilical vein endotheilial cells; DCFH-DA, 2’7′-dichlorofluorescin-diacetate; H2O2, hydrogen peroxide; nitric oxide, NO; RNS, reactive nitrogen species; DPI, diphenylene iodonium; NAC, Nacetylcysteine;E(3 6 0m M) + NA C (1 0m M) +7 EmM )+((mM )+ NA CENA CFigure 5 synthesis Antioxidant N-acetylcysteine blocks estrogen-induced DNA Antioxidant N-acetylcysteine blocks estrogen-induced DNA synthesis. Human umbilical vein endothelial cells pretreated with the antioxidant N-acetylcysteine (NAC) showed a significant reduction in E2-induced DNA synthesis. Data from three independent experiments are presented as ROS production with controls set at 100 (?SD). Values that are significantly different from E2 treatment alone (P < 0.05) are indicated with an asterisk (*). Significant increases in DNA synthesis by E2 (P < 0.05) are indicated by (#).NA C(Competing interestsThe author(s) declare that they have no competing interests.Authors' contributionsThe author has contributed to the design of the study, the data analysis, and the writing of the manuscript.Acknowledgementscan be blocked with H2O2 scavenging compounds NAC (Figure 2) and ebselen (Figure 3); the identity of the E2induced oxidant appears to be H2O2. Our data is corroborated by studies showing that H2O2 increases, while antioxidants such as catalase, sodium pyruvate, and superoxide dismutase decrease HUVECs cell growth [37]. In experimental animals, selectively overproducing or removing H2O2 significantly altered atherogenesis [38]. We previously showed that E2 exposure increases the growth of macrophages and the secretion of the proinflammatory cytokine TNF- [10,39]. Taken together, these data suggest that endothelial cells produce ROS in response to E2 or indirectly in response to E2-induced cytokines. Atherosclerotic lesions have been proposed to occur as a result of the monoclonal expansion of a mutated vascular cell [40]. Thus, E2-induced ROS in endothelial cells may be an underlying mechanism for the development of vascular lesions.We highly appreciate the technical assistance of Adam Leisy with the culture of HUVECs, measurement of ROS, and measurement of BrdU incorporation.
Ogorevc et al. Journal of.