Tyrphostin AG490 reduces NAPDH oxidase activity and expression in the aorta of hypercholesterolemic apolipoprotein E-deficient mice

Fenyo, Ioana Mădălina; Florea, Irina C.; Raicu, Monica; Manea, Adrian

doi:10.1016/j.vph.2011.03.006

Cited by 38 publications

(21 citation statements)

References 40 publications

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“…This finding suggests that NOX1-derived production of ROS induced by 5-FU causes the upregulation of TNF-␣ in macrophages located in the lamina propria of intestinal mucosa, consequently triggering apoptotic mechanisms, including the activation of caspase-3 and caspase-8 in the intestinal crypt. While several studies have demonstrated that NOX1 is expressed in intestinal epithelial cells (18,42), expression of both NOX1 and NOX2 was recently observed in the murine monocyte/macrophage cell line RAW264.7 (11,20). Interestingly, we also detected NOX1 mRNA expression in isolated peritoneal macrophages, and this expression was upregulated by lipopolysaccharide (data not shown), suggesting a possibility that NOX1 expressed in inflammatory cells may be involved in the pathogenesis of intestinal mucositis.…”

Section: Discussioncontrasting

confidence: 45%

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Yasuda

Kato

Yamanaka

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice. Am J Physiol Gastrointest Liver Physiol 302: G1133-G1142, 2012. First published March 7, 2012 doi:10.1152/ajpgi.00535.2011.-Although NADPH oxidase 1 (NOX1) has been shown to be highly expressed in the gastrointestinal tract, the physiological and pathophysiological roles of this enzyme are not yet fully understood. In the present study, we investigated the role of NOX1 in the pathogenesis of intestinal mucositis induced by the cancer chemotherapeutic agent 5-fluorouracil (5-FU) in mice. Intestinal mucositis was induced in Nox1 knockout (Nox1KO) and littermate wild-type (WT) mice via single, daily administration of 5-FU for 5 days. In WT mice, 5-FU caused severe intestinal mucositis characterized by a shortening of villus height, a disruption of crypts, a loss of body weight, and diarrhea. In Nox1KO mice, however, the severity of mucositis was significantly reduced, particularly with respect to crypt disruption. The numbers of apoptotic caspase-3-and caspase-8-activated cells in the intestinal crypt increased 24 h after the first 5-FU administration but were overall significantly lower in Nox1KO than in WT mice. Furthermore, the 5-FU-mediated upregulation of TNF-␣, IL-1␤, and NOX1 and the production of reactive oxygen species were significantly attenuated in Nox1KO mice compared with that in WT mice. These findings suggest that NOX1 plays an important role in the pathogenesis of 5-FU-induced intestinal mucositis. NOX1-derived ROS production following administration of 5-FU may promote the apoptotic response through upregulation of inflammatory cytokines.

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Section: Discussioncontrasting

confidence: 45%

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Yasuda

Kato

Yamanaka

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…These results were consistent with previous clinical and animal studies (24,25). Hcy levels have been reported to be higher in patients with essential hypertension compared with normotensive subjects, with higher levels of Hcy being associated with an increased risk of hypertension (26).…”

Section: Discussionsupporting

confidence: 93%

Vascular protective effects of Astragalus membranaceus and its main constituents in rats with chronic hyperhomocysteinemia

Qiu

Zhang

Lian

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Hyperhomocysteinemia (HHcy) is an important factor in cardiovascular disease. However, is currently no cure available in western medicine for HHcy-evoked cardiovascular disease. The present study explored the vascular protective effects of Astragalus membranaceus (AM), a traditional Chinese medicine. Rats with HHcy were induced by feeding high-methionine diets and treated with total extract of AM (TEA) and its constituents, including Astragalus saponins (ASP), Astragalus total flavonoids (ATF) and Astragalus polysaccharides (APS). Examination of the rats indicated that TEA and ASP controlled blood pressure and ameliorated HHcy-induced impairment of endothelium-dependent vasorelaxation by increasing the nitric oxide content and nitric oxide synthase activity of the abdominal aorta. Furthermore, they decreased the accumulation of hydrogen peroxide and superoxide anion, and attenuated the inhibition of superoxide dismutase and catalase activities in rats with HHcy. Additionally, TEA and ASP attenuated the HHcy-induced increases of matrix metalloproteinase (MMP)-2 and -9 concentrations. However, similar effects were not observed for ATF and APS. In conclusion, TEA and ASP are beneficial to vascular disease, and their effects may be attributed to protective actions against oxidation, activity of the MMPs and endothelial dysfunction.

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“…314 Finally, a study using the janus kinase-2 inhibitor tyrphostin AG490 found that in ApoE -/- mice fed a high fat diet, Nox1, 2 and 4 were elevated in the aorta, and that treatment with the inhibitor reduced expression and activity of all three homologues and reduced lesion area. 315 …”

Section: Physiology and Pathophysiology In Vivomentioning

confidence: 99%

Biochemistry, Physiology, and Pathophysiology of NADPH Oxidases in the Cardiovascular System

Lassègue

Martín

Griendling

2012

Circulation Research

679

749

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The NADPH oxidase (Nox) enzymes are critical mediators of cardiovascular physiology and pathophysiology. These proteins are expressed in virtually all cardiovascular cells, and regulate such diverse functions as differentiation, proliferation, apoptosis, senescence, inflammatory responses and oxygen sensing. They target a number of important signaling molecules, including kinases, phosphatases, transcription factors, ion channels and proteins that regulate the cytoskeleton. Nox enzymes have been implicated in many different cardiovascular pathologies: atherosclerosis, hypertension, cardiac hypertrophy and remodeling, angiogenesis and collateral formation, stroke and heart failure. In this review, we discuss in detail the biochemistry of Nox enzymes expressed in the cardiovascular system (Nox1, 2, 4 and 5), their roles in cardiovascular cell biology, and their contributions to disease development.

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Tyrphostin AG490 reduces NAPDH oxidase activity and expression in the aorta of hypercholesterolemic apolipoprotein E-deficient mice

Cited by 38 publications

References 40 publications

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Vascular protective effects of Astragalus membranaceus and its main constituents in rats with chronic hyperhomocysteinemia

Biochemistry, Physiology, and Pathophysiology of NADPH Oxidases in the Cardiovascular System

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