Pugazhenthi S, Akhov L, Selvaraj G, Wang M, Alam J. Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse  cells. Am J Physiol Endocrinol Metab 293: E645-E655, 2007. First published May 29, 2007 doi:10.1152 doi:10. /ajpendo.00111.2007, a component of turmeric, has been shown to have therapeutic properties. Induction of phase 2 detoxifying enzymes is a potential mechanism through which some of the actions of curcumin could proceed. Heme oxygenase-1 (HO-1), an antioxidant phase 2 enzyme, has been reported to have cytoprotective effects in pancreatic -cells. Curcumin on further purification yields demethoxy curcumin (DMC) and bisdemethoxy curcumin (BDMC). The objective of the present study was to determine the mechanism by which these purified curcuminoids induce HO-1 in MIN6 cells, a mouse -cell line. Demethoxy curcuminoids induced HO-1 promoter linked to the luciferase reporter gene more effectively than curcumin. The induction was dependent on the presence of antioxidant response element (ARE) sites containing enhancer regions (E1 and E2) in HO-1 promoter and nuclear translocation of nuclear factor-E2-related factor (Nrf2), the transcription factor that binds to ARE. Curcuminoids stimulated multiple signaling pathways that are known to induce HO-1. Inhibition of specific signaling pathways with pharmacological inhibitors and cotransfection experiments suggested the involvement of phosphotidylinositol 3-kinase and Akt. Real-time quantitative RT-PCR analysis showed significant elevation in the mRNA levels of HO-1 and two other phase 2 enzymes, the regulatory subunit of glutamyl cysteine ligase, which is needed for the synthesis of glutathione, and NAD(P)H:quinone oxidoreductase, which detoxifies quinones. DMC and BDMC induced the expression of HO-1 and translocated Nrf2 to nucleus in -cells of mouse islets. Our observations suggest that demethoxy curcuminoids could be used to induce a cellular defense mechanism in -cells under conditions of stress as seen in diabetes. phase 2 enzymes; diabetes; pancreatic -cells; oxidative stress PHASE 1 AND PHASE 2 ENZYMES are involved in cellular defense against oxidative stress and xenobiotic insult (42). The electrophiles generated by phase 1 enzymes (such as cytochrome P-450s) are scavenged by phase 2 enzymes including heme oxygenase (HO)-1, ␥-glutamylcysteine ligase (GCL), glutathione S-transferase, and NAD(P)H:quinone oxidoreductase (NQO1) (38). Heme oxygenases catalyze the rate-limiting step of heme degradation, producing equimolar quantities of carbon monoxide (CO), Fe 2ϩ , and biliverdin. Biliverdin is then converted to bilirubin by bilirubin reductase. HO-2 is the constitutively active form, and HO-1 is the inducible form. In addition to its role in the metabolism of heme, HO-1 has emerged as an important mediator of cellular defense against wide-ranging tissue injuries (44). Embryonic fibroblasts isolated from mice deficient in HO-1 have been shown to be susceptible to oxidative injury resul...
Proanthocyanidin biosynthesis in the seed coat of yellow-seeded, canola quality Brassica napus YN01-429 is constrained at the committed step catalyzed by dihydroflavonol 4-reductase Akhov, Leonid; Ashe, Paula; Tan, Yifang; Datla, Raju; Selvaraj, Gopalan Proanthocyanidin biosynthesis in the seed coat of yellow-seeded, canola quality Brassica napus YN01-429 is constrained at the committed step catalyzed by dihydroflavonol 4-reductase 1 Leonid Akhov, Paula Ashe, Yifang Tan, Raju Datla, and Gopalan Selvaraj Abstract: The yellow seed characteristic in Brassica napus L. is desirable because of its association with higher oil content and better quality of oil-extracted meal. YN01-429 is a yellow-seeded canola-quality germplasm developed in Canada arising from several years of research. Seed-coat pigmentation is due to oxidized proanthocyanidins (PA; condensed tannins) derived from phenylpropanoids and malonyl CoA. We found PA accumulation to be most robust in young seed coats (20 d post anthesis; dpa) of a related black-seeded line N89-53 and only very little PA in YN01-429, which also contained much less extractable phenolics. The flavonol content, however, did not show as great a difference between these two lines. Furthermore, sinapine, a product of the general phenylpropanoid metabolism, was present at comparable levels in the embryos of both lines. Dihydroflavonol reductase (DFR) activity that commits phenolics to PA synthesis was lower in YN01-429 seed coats. The results of Southern blot and in silico analyses were indicative of two copies of the DFR gene in B. napus. Both copies were functional in YN01-429, ruling out homeoallelic repression or silencing, but together they showed very low expression levels (17-fold fewer transcripts) relative to DFR activity in N89-53 seed coats. These results collectively suggest that YN01-429 differs in regulatory circuits that impact the PA synthesis branch much more than the flavonol synthesis branch in the seed coats and such circuits do not impinge upon general phenylpropanoid metabolism in the embryos.Key words: condensed tannin, dihydroflavonol reductase, flavonoids, oilseed rape, rapeseed, transparent testa. Résumé :Le jaune caractéristique des grains du Brassica napus L. est désirable, compte tenu de son association avec une haute teneur en huile et une meilleure qualité de la farine extraite de l'huile. Le YN01-429 constitue un germplasme à graine jaune de qualité canola résultant de plusieurs années de recherches. La pigmentation des téguments est attribuéeà des proanthocyanidines oxydées (PA; tannins condensés) dérivées de phénylpropanoïdes et du CoA du malonyl. Les auteurs ont trouvé une plus forte accumulation de PA chez les jeunes téguments (20 jours après l'anthèse; dpa) d'une lignée apparentéeà grains noirs N89-53 et très peu de PA chez la lignée YN01-429 qui contient à la fois beaucoup moins de phénols extractibles. Cependant, la teneur en flavonols ne montre pas autant de différences entre ces deux lignées. De plus, la sinapine, un produit du métabolisme géné...
Our observations suggest that curcumin or its analogues could be used to induce cellular defense against oxidative stress and improve islet transplantation outcomes.
The flowers of flax (linseed) are blue-hued, ephemeral and self-pollinating, and the seeds are typically brown. A century-old interest in natural yellow seed variants and a historical model point to recessive alleles in B1, D and G loci being responsible, but the functional aspects had remained unknown. Here, we characterized the “D” locus by quantitative trait loci (QTL) mapping and identified a FLAVONOID 3′5′ HYDROXYLASE (F3′5′H) gene therein. It does not belong to the F3′5′H clade, but resembles biochemically characterized F3′Hs (flavonoid 3′ hydroxylase) but without F3′H activity. The genome lacks other F3′H or F3′H-like genes. The apparent neo-functionalization from F3′H is associated with a Thr498 → Ser498 substitution in a substrate recognition site (SRS). The yellow seed and white flower phenotypes of the classical d mutation was found to be due to one nucleotide deletion that would truncate the deduced product and remove three of the six potential SRS, negatively impacting delphinidin synthesis. Delphinidin is sporadic in angiosperms, and flax has no known pollination syndrome(s) with functional pollinator group(s) that are attracted to blue flowers, raising questions on the acquisition of F3′5′H. The appearance of d allele is suggestive of the beginning of the loss of F3′5′H in this species.
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