Ca2+-Dependent NOX5 (NADPH Oxidase 5) Exaggerates Cardiac Hypertrophy Through Reactive Oxygen Species Production.

NOX5 (NADPH oxidase 5) is a homolog of the gp91phox subunit of the phagocyte NOX, which generates reactive oxygen species. NOX5 is involved in sperm motility and vascular contraction and has been implicated in diabetic nephropathy, atherosclerosis, and stroke. The function of NOX5 in the cardiac hypertrophy is unknown. Because NOX5 is a Ca2+-sensitive, procontractile NOX isoform, we questioned whether it plays a role in cardiac hypertrophy. Studies were performed in (1) cardiac tissue from patients undergoing heart transplant for cardiomyopathy and heart failure, (2) NOX5-expressing rat cardiomyocytes, and (3) mice expressing human NOX5 in a cardiomyocyte-specific manner. Cardiac hypertrophy was induced in mice by transverse aorta coarctation and Ang II (angiotensin II) infusion. NOX5 expression was increased in human failing hearts. Rat cardiomyocytes infected with adenoviral vector encoding human NOX5 cDNA exhibited elevated reactive oxygen species levels with significant enlargement and associated increased expression of ANP (atrial natriuretic peptides) and ß-MHC (ß-myosin heavy chain) and prohypertrophic genes (Nppa, Nppb, and Myh7) under Ang II stimulation. These effects were reduced by N-acetylcysteine and diltiazem. Pressure overload and Ang II infusion induced left ventricular hypertrophy, interstitial fibrosis, and contractile dysfunction, responses that were exaggerated in cardiac-specific NOX5 trangenic mice. These phenomena were associated with increased reactive oxygen species levels and activation of redox-sensitive MAPK (mitogen-activated protein kinase). N-acetylcysteine treatment reduced cardiac oxidative stress and attenuated cardiac hypertrophy in NOX5 trangenic. Our study defines Ca2+-regulated NOX5 as an important NOX isoform involved in oxidative stress- and MAPK-mediated cardiac hypertrophy and contractile dysfunction.

Hepatocyte TNF Receptor-Associated Factor 6 Aggravates Hepatic Inflammation and Fibrosis by Promoting Lysine 6-Linked Polyubiquitination of Apoptosis Signal-Regulating Kinase 1.

Activation of apoptosis signal-regulating kinase 1 (ASK1) is a key driving force of the progression of nonalcoholic steatohepatitis (NASH) and represents an attractive therapeutic target for NASH treatment. However, the molecular and cellular mechanisms underlying ASK1 activation in the pathogenesis of NASH remain incompletely understood. In this study, our data unequivocally indicated that hyperactivated ASK1 in hepatocytes is a potent inducer of hepatic stellate cell (HSC) activation by promoting the production of hepatocyte-derived factors. Our previous serial studies have shown that the ubiquitination system plays a key role in regulating ASK1 activity during NASH progression. Here, we further demonstrated that tumor necrosis factor receptor-associated factor 6 (TRAF6) promotes lysine 6 (Lys6)-linked polyubiquitination and subsequent activation of ASK1 to trigger the release of robust proinflammatory and profibrotic factors in hepatocytes, which, in turn, drive HSC activation and hepatic fibrosis. Consistent with the in vitro findings, diet-induced liver inflammation and fibrosis were substantially attenuated in Traf6+/- mice, whereas hepatic TRAF6 overexpression exacerbated these abnormalities. Mechanistically, Lys6-linked ubiquitination of ASK1 by TRAF6 facilitates the dissociation of thioredoxin from ASK1 and N-terminal dimerization of ASK1, resulting in the boosted activation of ASK1-c-Jun N-terminal kinase 1/2 (JNK1/2)-mitogen-activated protein kinase 14(p38) signaling cascade in hepatocytes. Conclusion: These results suggest that Lys6-linked polyubiquitination of ASK1 by TRAF6 represents a mechanism underlying ASK1 activation in hepatocytes and a key driving force of proinflammatory and profibrogenic responses in NASH. Thus, inhibiting Lys6-linked polyubiquitination of ASK1 may serve as a potential therapeutic target for NASH treatment.

Cavity-enhanced optical controlling based on three-wave mixing in cavity-atom ensemble system.

Cavity-enhanced optical controlling is experimentally observed with a low-control laser power in a cavity-atom ensemble system. Here, the three-level atoms are coupled with two optical modes of a Fabry-Perot cavity, where a new theoretical model is developed to describe the effective three-wave mixing process between spin-wave and optical modes. By adjusting either temperature or cavity length, we demonstrate the precise frequency tuning of the hybrid optical-atomic resonances. When the doubly-resonant condition is satisfied, the probe laser can be easily modulated by a control laser. In addition, interesting non-Hermitian physics are predicted theoretically and demonstrated experimentally, and all-optical switching is also achieved. Such a doubly-resonant cavity-atom ensemble system without a specially designed cavity can be used for future applications, such as optical signal storage and microwave-to-optical frequency conversion.

Stability-increasing effects of anthocyanin glycosyl acylation.

This review comprehensively summarizes the existing knowledge regarding the chemical implications of anthocyanin glycosyl acylation, the effects of acylation on the stability of acylated anthocyanins and the corresponding mechanisms. Anthocyanin glycosyl acylation commonly refers to the phenomenon in which the hydroxyl groups of anthocyanin glycosyls are esterified by aliphatic or aromatic acids, which is synthetically represented by the acylation sites as well as the types and numbers of acyl groups. Generally, glycosyl acylation increases the in vitro and in vivo chemical stability of acylated anthocyanins, and the mechanisms primarily involve physicochemical, stereochemical, photochemical, biochemical or environmental aspects under specific conditions. Additionally, the acylation sites as well as the types and numbers of acyl groups influence the stability of acylated anthocyanins to different degrees. This review could provide insight into the optimization of the stability of anthocyanins as well as the application of suitable anthocyanins in food, pharmaceutical and cosmetic industries.

[Contents and the Correlations of the Total Anthocyanins and Saponins of the Vegetative Organs of Panax notoginseng with Purple and Green Aerial Stems at Different Growth Stages].

Objective: To study the accumulation characteristics of total anthocyanins and saponins in the vegetative organ of Panax notoginseng with purple and green aerial stems at different growth stages. Methods: The contents of the total anthocyanins and saponins of the leaves, aerial stems, rhizomes and the adventitious roots of one-, two- and three-year-old Panax notoginseng with purple and green aerial stems were determined by spectrophotometry. Results: From one-year-old to three-year-old Panax notoginseng, the total anthocyanin contents (TACs) of the leaves, aerial stems and all vegetative organs and the percentages of the aerial stems TACs to those of all vegetative organs of purple aerial stemmed Panax notoginseng plants, the percentages of the total saponin contents (TSCs) of the leaves and aerial stems to those of all vegetative organs of the purple and green aerial stemmed plants and the percentages of the leaves TACs to those of vegetative organs of the green aerial stemmed plants all decreased. The TACs of the leaves and all vegetative organs of the green aerial stemmed plants, the TACs of the rhizomes and their adventitious roots, the vegetative organ TSCs and the percentages of the TSCs of the rhizomes and their adventitious roots to those of all vegetative organs of the purple and green aerial stemmed plants, and the percentages of the TACs of the rhizomes and their adventitious roots to those of all vegetative organs of the purple aerial stemmed plants were increased. The increasing rates of the TACs of the aerial stems and all vegetative organs and the TSCs of the aerial stems, rhizomes and their adventitious roots and all vegetative organs of the purple aerial stemmed plants were always higher than those of the green aeria stemmed plants, but the increasing rates of the leaves TSCs were lower than those of the green aerial stemmed plants, and the content changes of the vegetative organ TACs and TSCs of the purple and green aerial stemmed plants exhibited different correlations. Additionally, the three-years-old plants, the TSCs of the vegetative organs of the purple aerial stemmed plants were all higher than those of the green aerial stemmed plants, but the TACs of the leaves and rhizomes and their adventitious roots were lower than those of the green aerial stemmed plants. Conclusion: The saponin-accumulating capacity of the vegetative organs of purple aerial stemmed Panax notoginseng plants is stronger than that of green aerial stemmed Panax notoginseng.

Bioinformatics analysis of the squalene synthase gene and the amino acid sequence in ginseng species.

The cDNA sequence, their structure, physical properties, signal peptide, hydrophobicity, hydrophilicity, subcellular localization domain of transmembrane domain and evolutionary relationship of encoded amino acid sequences were analyzed in squalene synthase of 9 species of ginseng plant using bioinformatics methods on GenBank. The results showed that the averaged similarity of squalene synthase cDNA sequence structure in Ginseng species was 96.245%, the similarity of the amino acid encoding sequence was 95.5%. The secondary structure prediction results showed that the amino acid sequence of 9 squalene synthase had α helix and random coil as the main components. After the phylogenetic analysis in 9 kinds of ginseng species, we found that they can be divided into two subfamilies. The analysis showed that plants, animals, yeasts belonged to different species, the homology was high within plant species and animal species. By analyzing the ginseng species squalene synthase and their encoding gene bioinformatics features, we can provide the theoretical reference for the squalene synthase gene cloning and the genetic manipulation.

Molecular structures of the stem tuber anthocyanins of colored potatoes and their coloring effects on the tubers.

This paper summarized the important achievements about the general characteristics of the molecular structures of the stem tuber anthocyanins of Colored potatoes and the basic coloring effects of the anthocyanins on the tubers. The various coloration patterns of the skins and/or flesh of Colored potato tubers result from the accumulation of the anthocyanins in the periderms, phelloderms and/or peripheral cortices of the tubers, and the tuber colors are fundamentally determined by the matching profiles of the six naturally occurring anthocyanidins, i.e., cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin. Generally, the tuber anthocyanidins hold an O-glycosidic bond-linked rutinosyl at the C3 site, and either a glucosyl linked by an O-glycosidic bond or no substituent group may exist at the C5 site simultaneously. Furthermore, an E-monoacyl frequently exists at the C3-rutinosyls or at the C5-glucosyls of most tuber anthocyanins, and the phenolic acids acylating the tuber anthocyanins are often p-coumaric, ferulic and caffeic acids. The popular names of the p- coumaric acid derivatives of the malvidin, pelargonidin, peonidin and petunidin of the tubers are Malvanin, Pelanin, Peonanin and Petanin, respectively. This review provides a reference for the exploration of the mechanism of the tuber coloration and the identification of the molecular structures of the stem tuber anthocyanins of Colored potatoes.

Structure-activity relationships of anthocyanidin glycosylation.

This paper summarizes the main achievements about the structure-activity relationships of anthocyanidin glycosylation. Anthocyanidin glycosylation is the essential step of anthocyanin biosynthesis and also the prerequisite of the further modifications of anthocyanins, which is jointly characterized by the glycosylation site, the type and number of the glycosyl as well as the glycosidic bond type. It generally enhances the stability, results in the hypsochromic effect and blueing, decreases the bioavailability and anticancer activity, and decreases, increases, or does not change the antioxidant activity of the anthocyanidins or anthocyanins, which is synergetically determined by the glycosylation site and the type and number of the glycosyl. Thereinto, in nature, the blue hues caused by the glycosylation may also be reinforced by the formation of the anthocyanic vacuolar inclusions. This review could provide a reference for the research of the structure-optimizing and function-exploiting of anthocyanins.

[Contents of total anthocyanins and total saponins as well as composition of saponin monomers of Purple and Green Notoginseng Radix et Rhizoma].

OBJECTIVE: The contents of total anthocyanins and total saponins as well as the composition of saponin monomers of Purple and Green Notoginseng Radix et Rhizoma were studied to compare the medicinal quality and commercial values. METHODS: Three-year-old Notoginseng Radix et Rhizoma was selected as the research materials. The contents of total anthocyanins and total saponins were determined by spectrophotometry. The compositions of saponin monomers were monitored by HPLC. The significance of content differences was determined by variance analysis. RESULTS: The contents of total anthocyanins and total saponins of Purple Notoginseng Radix et Rhizomawere about 204.85% and 33.86% higher than those of Green Notoginseng Radix et Rhizoma respectively. The Purple and Green Notoginseng Radix et Rhizoma both contained five saponin monomers whose contents were as follows: ginsenoside Rg1 > ginsenoside Rb1 > notoginsenoside R1 > ginsenoside Rd > ginsenoside Re. The contents of notoginsenoside R1, ginsenoside Rd and ginsenoside Re of Purple Notoginseng Radix et Rhizoma were about 16.03%, 10.83% and 5.39% higher than those of Green Notoginseng Radix et Rhizoma respectively. However, the contents of ginsenoside Rg1 and ginsenoside Rb1 of Green Notoginseng Radix et Rhizoma were about 0.93% and 3.33% higher than those of Purple Notoginseng Radix et Rhizoma respectively. With respect to Green Notoginseng Radix et Rhizoma, the increase of the total anthocyanins in Purple Notoginseng Radix et Rhizoma reached a significant level, but the increases of total saponins, notoginsenoside R1, ginsenoside Rd and ginsenoside Re and the decreases of ginsenoside Rg1 and ginsenoside Rb1 did not. CONCLUSION: The total anthocyanins accumulation in Notoginseng Radix et Rhizoma implies the content increases of the total saponins, notoginsenoside R1, ginsenoside Rd and ginsenoside Re, and the slight decreases of ginsenoside Rg1 and ginsenoside Rb1 contents; but the type and relative contents of saponin monomers remain unchanged. The medicinal quality and commercial value of Purple Notoginseng Radix et Rhizoma are higher than those of Green Notoginseng Radix et Rhizoma.

Key enzymes of triterpenoid saponin biosynthesis and the induction of their activities and gene expressions in plants.

Triterpenoid saponins are one of the key active components of many medicinal plants. The biosynthetic pathway of triterpenoid saponins in higher plants and a lot of experimental results both indicated that the key enzymes involved in triterpenoid saponin synthesis are squalene synthase (SS), squalene epoxidase (SE), lupeol synthase (LS), dammarenediol synthase (DS), beta-amyrin synthase (beta-AS), cytochrome P450-dependent monooxygenase (PDMO), and glycosyltransferase (GT). The activities and coding genes of the key enzymes could be induced by a range of factors in various plant species. However, the effects of the factors on the content and composition of the triterpenoid saponins in specific plants are not certainly coincident, and different factors appear to induce the gene expressions of the key enzymes by different signal pathways and at different levels. This paper could provide a reference for strengthening the triterpenoid saponin-synthesizing capability of specific medicinal plants at enzyme and/or gene expression levels in order to improve the plants' commercial values.