NAD(P)H Dehydrogenase (Quinone)

Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Conversion of cholesterol to bile acids in the liver is initiated by the rate-limiting enzyme cholesterol 7alpha-hydroxylase (CYP7A1) and excretion of bile acids from the liver is mediated by the bile salt export pump (BSEP). The expression of CYP7A1 and BSEP is coordinately regulated by a negative feedback and positive feed-forward mechanism, respectively, through bile acid-mediated activation of farsenoid X receptor (FXR). It is well established that hypolipidemic agent guggulsterone is an FXR antagonist and down-regulates FXR target genes.

Author(s): 
Deng, Ruitang
Yang, Dongfang
Radke, Amy
Yang, Jian
Yan, Bingfang
Publication Title: 
Chemical Research in Toxicology

The roots of Angelica sinensis (Oliv.) Diels (Dang Gui; Apiaceae) have a long history in traditional Chinese medicine as a remedy for women's disorders and are often called "lady's ginseng". Currently, extracts of A. sinensis are commonly included in numerous dietary supplements used for women's health and as antiaging products. In the present study, we examined the potential chemopreventive activity of A. sinensis extracts by measuring the relative ability to induce the detoxification enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1).

Author(s): 
Dietz, Birgit M.
Liu, Dongting
Hagos, Ghenet K.
Yao, Ping
Schinkovitz, Andreas
Pro, Samuel M.
Deng, Shixin
Farnsworth, Norman R.
Pauli, Guido F.
van Breemen, Richard B.
Bolton, Judy L.
Publication Title: 
American Journal of Physiology. Heart and Circulatory Physiology

Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. Resveratrol was also shown to confer vasoprotection in animal models of type 2 diabetes and aging. However, the mechanisms by which resveratrol exerts its antioxidative vasculoprotective effects are not completely understood.

Author(s): 
Ungvari, Zoltan
Bagi, Zsolt
Feher, Attila
Recchia, Fabio A.
Sonntag, William E.
Pearson, Kevin
de Cabo, Rafael
Csiszar, Anna
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Nonalcoholic fatty liver disease (NAFLD), which occurs in approximately 17 to 40% of Americans, encompasses progressive stages of liver damage ranging from steatosis to nonalcoholic steatohepatitis (NASH). Inflammation and oxidative stress are known characteristics of NAFLD; however, the precise mechanisms occurring during disease progression remain unclear.

Author(s): 
Hardwick, Rhiannon N.
Fisher, Craig D.
Canet, Mark J.
Lake, April D.
Cherrington, Nathan J.
Publication Title: 
Analytical Chemistry

Inhibitors of quinone reductase-2 (NQO2; QR-2) can have antimalarial activity and antitumor activities or can function as chemoprevention agents by preventing the metabolic activation of toxic quinones such as menadione. To expedite the search for new natural product inhibitors of QR-2, we developed a screening assay based on ultrafiltration liquid chromatography-mass spectrometry that is compatible with complex samples such as bacterial or botanical extracts.

Author(s): 
Choi, Yongsoo
Jermihov, Katherine
Nam, Sang-Jip
Sturdy, Megan
Maloney, Katherine
Qiu, Xi
Chadwick, Lucas R.
Main, Matthew
Chen, Shao-Nong
Mesecar, Andrew D.
Farnsworth, Norman R.
Pauli, Guido F.
Fenical, William
Pezzuto, John M.
van Breemen, Richard B.
van Breemen, Richard R.
Publication Title: 
American Journal of Physiology. Heart and Circulatory Physiology

Hyperglycemia in diabetes mellitus promotes oxidative stress in endothelial cells, which contributes to development of cardiovascular diseases. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor activated by oxidative stress that regulates expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes. This study was designed to elucidate the homeostatic role of adaptive induction of Nrf2-driven free radical detoxification mechanisms in endothelial protection under diabetic conditions.

Author(s): 
Ungvari, Zoltan
Bailey-Downs, Lora
Gautam, Tripti
Jimenez, Rosario
Losonczy, Gyorgy
Zhang, Cuihua
Ballabh, Praveen
Recchia, Fabio A.
Wilkerson, Donald C.
Sonntag, William E.
Pearson, Kevin
de Cabo, Rafael
Csiszar, Anna
Publication Title: 
American Journal of Physiology. Heart and Circulatory Physiology

There is strong evidence showing that aging is associated with vascular oxidative stress, which has been causally linked to the development of cardiovascular diseases. NF-E2-related factor-2 (Nrf2) is a transcription factor, which is activated by reactive oxygen species in the vasculature of young animals leading to the upregulation of various antioxidant genes. The present study was designed to elucidate age-related changes in the homeostatic role of Nrf2-driven free radical detoxification mechanisms in the vasculature.

Author(s): 
Ungvari, Zoltan
Bailey-Downs, Lora
Sosnowska, Danuta
Gautam, Tripti
Koncz, Peter
Losonczy, Gyorgy
Ballabh, Praveen
de Cabo, Rafael
Sonntag, William E.
Csiszar, Anna
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Recent studies demonstrate that age-related dysfunction of NF-E2-related factor-2 (Nrf2)-driven pathways impairs cellular redox homeostasis, exacerbating age-related cellular oxidative stress and increasing sensitivity of aged vessels to oxidative stress-induced cellular damage. Circulating levels of insulin-like growth factor (IGF)-1 decline during aging, which significantly increases the risk for cardiovascular diseases in humans.

Author(s): 
Bailey-Downs, Lora C.
Mitschelen, Matthew
Sosnowska, Danuta
Toth, Peter
Pinto, John T.
Ballabh, Praveen
Valcarcel-Ares, M. Noa
Farley, Julie
Koller, Akos
Henthorn, Jim C.
Bass, Caroline
Sonntag, William E.
Ungvari, Zoltan
Csiszar, Anna
Publication Title: 
Antioxidants & Redox Signaling

AIMS: Pulmonary oxygen toxicity contributes to lung injury in newborn and adult humans. We previously reported that thioredoxin reductase (TrxR1) inhibition with aurothioglucose (ATG) attenuates hyperoxic lung injury in adult mice. The present studies tested the hypothesis that TrxR1 inhibition protects against the effects of hyperoxia via nuclear factor E2-related factor 2 (Nrf2)-dependent mechanisms. RESULTS: Both pharmacologic and siRNA-mediated TrxR1 inhibition induced robust Nrf2 responses in murine-transformed Clara cells (mtCC).

Author(s): 
Locy, Morgan L.
Rogers, Lynette K.
Prigge, Justin R.
Schmidt, Edward E.
Arnér, Elias S. J.
Tipple, Trent E.
Publication Title: 
Molecular Nutrition & Food Research

SCOPE: Hops contain the phytoestrogen, 8-prenylnaringenin, and the cytoprotective compound, xanthohumol (XH). XH induces the detoxification enzyme, NAD(P)H-quinone oxidoreductase (NQO1) in vitro; however, the tissue distribution of XH and 8-prenylnaringenin and their tissue-specific activity have not been analyzed. METHODS AND RESULTS: An orally administered hop extract and subcutaneously injected XH were administered to Sprague-Dawley rats over 4 days. LC-MS-MS analysis of plasma, liver, and mammary gland revealed that XH accumulated in liver and mammary glands.

Author(s): 
Dietz, Birgit M.
Hagos, Ghenet K.
Eskra, Jillian N.
Wijewickrama, Gihani T.
Anderson, Jeffrey R.
Nikolic, Dejan
Guo, Jian
Wright, Brian
Chen, Shao-Nong
Pauli, Guido F.
van Breemen, Richard B.
Bolton, Judy L.

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