Action Of Carotenoids Research Articles

식물에서 Carotenoid 생합성 경로와 대사공학적 응용

Carotenoids are synthesized from the plastidic glyceraldehyde-3-phosphate (GAP)/pyruvate pathway in isoprenoids biosynthetic system of plants. They play a crucial role in light harvesting, work as photoprotective agents in photosynthesis of nature, and are also responsible for the red, orange and yellow colors of fruits and flowers in plants. In addition to biological actions of carotenoids as antioxidants and natural pigments, they are essential components of human diet as a source of vitamin A. It has been also suggested that some kinds of carotenoids might provide protection against cancer and heart disease as human medicines. In this article, we review the commercial applications on the basis of biological functions of carotenoids, summarize the studies of genes involved in the carotenoid biosynthetic pathway, and introduce recent results achieved in metabolic engineering of carotenoids. This effort for understanding the carotenoids metabolism will make us to increase the total carotenoid contents of crop plants, direct the carotenoid biosynthetic machinery towards other useful carotenoids, and produce a new array of carotenoids by further metabolizing the new precursors that are created when one or two key enzymes in carotenoid biosynthetic pathway are exchanged through gene manipulation in the near future.

Carotenoids and environmental stress in plants : Significance of carotenoid-mediated modulation of membrane physical properties

Carotenoids, apart of their antenna function in photosynthesis, play an important role in the mechanisms protecting the photosynthetic apparatus against various harmful environmental factors. They protect plants against overexcitation in strong light and dissipate the excess of absorbed energy, they scavenge reactive oxygen species formed during photooxidative stress and moderate the effect of extreme temperatures. One of the important factors involved in the protective action of carotenoids is their influence on the molecular dynamics of membranes. To obtain complex information about interactions between carotenoids and lipids in a membrane, different techniques were used. In this review, the data resulting from EPR–spin label spectrometry, 31P- and 13C-NMR, differential scanning calorimetry, and computer simulation of the membrane molecular dynamics are presented. The effects of selected, structurally different carotenoid species on various physical parameters of model and natural membranes are described and their relevance to protection against some environmental stresses are discussed.

Mitogenic and apoptotic signaling by carotenoids: involvement of a redox mechanism.

The potential for carotenoids to modulate tumor growth is currently under investigation. Although epidemiological studies evidence that a high intake of vegetables, rich in carotenoids, decreases cancer incidence and mortality, clinical trials demonstrate that supplementation of beta-carotene to chronic smokers or to asbestos workers increases the risk for lung cancer. These contradictory findings have renewed interest in elucidating the mechanism of action of carotenoids in biological systems. In this review, we show evidence for mitogenic and apoptotic effects of carotenoids and we support the hypothesis that these molecules may act as anticarcinogens or as procarcinogens through a redox mechanism. In particular, we report demonstrations for the anti-oxidant or pro-oxidant effects of carotenoids in vitro and in vivo, focusing our attention on the relationship existing between cell growth and redox status.

β-Carotene Does Not Change Markers of Enzymatic and Nonenzymatic Antioxidant Activity in Human Blood

In vitamin A–replete populations, increased concentrations of serum carotenoids have been associated with a decreased risk of degenerative diseases. The mechanism of action of carotenoids in determining antioxidant activity is largely unknown. The aim of the study was to examine the effect of carotenoid supplementation and spinach intake on erythrocyte enzyme antioxidant activities, serum or plasma nonenzymatic antioxidant concentrations, and concentrations of oxidatively damaged amino acids in plasma. Subjects received for 3 wk a basic diet (n = 10), a basic diet with a carotenoid supplement (n = 12) or with a spinach product (n = 12 per group), i.e., whole-leaf, minced, liquefied or liquefied spinach plus added dietary fiber. After 3 wk of dietary intervention, changes in serum or plasma concentrations of ascorbic acid, α-tocopherol, FRAP (ferric reducing ability of plasma) and uric acid and erythrocyte enzyme activities were assessed, and differences among experimental groups were tested. Consumption of spinach resulted in greater (P < 0.01) erythrocyte glutathione reductase activity and lower (P < 0.05) erythrocyte catalase activity and serum α-tocopherol concentration compared with the control group. Consumption of the carotenoid supplement led to lower α-tocopherol responses (P = 0.02) compared with the basic diet only. Our data suggest that the short-term changes in erythrocyte glutathione reductase activity and serum α-tocopherol concentration can be attributed to an increased carotenoid (lutein and zeaxanthin) intake, but β-carotene is unlikely to be a causative factor. Lower erythrocyte catalase activity after intervention with spinach products may be related to other constituents in spinach such as flavonoids.

Biophysical properties of carotenoids.

Carotenoids are important biological pigments that play vital roles in nutrition, vision, cellular differentiation, growth control, photooxidative protection, cell membrane stability, and photosynthesis. A number of recent review articles aim to evaluate the literature in this field and identify areas for further research, such as human clinical trials which serve to prevent or protect against serious health disorders. It is likely that more studies attempting to relate carotenoids to therapy of cancer, coronary heart disease, HIV infections, or light-sensitive diseases will be undertaken. These are exciting areas for the study of functions and actions of carotenoids in biological systems. However, it is essential that these investigations are based on reliable biophysical and chemical principles so that the biological effects of carotenoids can be explained at the molecular level.

Metabolites of dietary carotenoids as potential cancer preventive agents

Abstract

Carotenoids Regulate Gene Expression and Induce Differentiation and Growth Inhibition in Human Placental Cells. † 1900

Carotenoids, plant pigments that are common components of the human diet, have been shown to modulate growth and function in several normal and transformed cell types. Certain carotenoids, particularly β-carotene(βC), are precursors for the formation of retinoic acid (RA). Mammalian fetuses derive carotenoids entirely from the maternal circulation. We have examined carotenoid placental uptake and cellular effects using primary cultures of human villous tissue and trophoblastic cells and a trophoblastic cell line (BeWo b30). Uptake of the carotenoids βC,β-apo-8′-carotenal and canthaxanthin (CTX) from organic solvent, carotenoid-loaded liposomes and human plasma lipoprotein fractions was saturable with respect to time and concentration. Rank order efficiency of uptake was LDL>HDL>liposomes> >solvent, suggesting that placental carotenoid uptake principally occurs via lipoprotein receptor-mediated endocytosis. Among 8 carotenoids of dietary importance or structural interest tested, βC and CTX inhibited cell proliferation in a time-and dose(1pM-1μM)-dependent fashion. βC and CTX increased steady state mRNA accumulations of α- and β-hCG, which are markers of trophoblast endocrine differentiation. Treatment withβ-apo-8′-carotenal (a previtamin A βC metabolite) had no effect upon trophoblast cell proliferation or hCG expression. These results suggest that certain placental actions of carotenoids are independent of conversion to RA. We also have examined trophoblast gene expression by RT-PCR differential display using unstimulated, βC-differentiated and RA-stimulated trophoblast mRNAs. We have identified 12 partial cDNAs whose abundance is regulated coordinately by βC and RA as well as 8 cDNAs which are upregulated only by βC, further indicating that carotenoids may alter gene expression via novel mechanisms. These carotenoid-induced changes in trophoblast growth and function may shed light on fetal micronutrient accumulation and on the observed relationship between carotenoid-deficient diets and the occurrence of pregnancy complications.

Structure and properties of carotenoids in relation to function.

The basic principles of structure, stereochemistry, and nomenclature of carotenoids are described and the relationships between structure and the chemical and physical properties on which all the varied biological functions and actions of carotenoids depend are discussed. The conjugated polyene chromophore determines not only the light absorption properties, and hence color, but also the photochemical properties of the molecule and consequent light-harvesting and photoprotective action. The polyene chain is also the feature mainly responsible for the chemical reactivity of carotenoids toward oxidizing agents and free radicals, and hence for any antioxidant role. In vivo, carotenoids are found in precise locations and orientations in subcellular structures, and their chemical and physical properties are strongly influenced by other molecules in their vicinity, especially proteins and membrane lipids. In turn, the carotenoids influence the properties of these subcellular structures. Structural features such as size, shape, and polarity are essential determinants of the ability of a carotenoid to fit correctly into its molecular environment to allow it to function. A role for carotenoids in modifying structure, properties, and stability of cell membranes, and thus affecting molecular processes associated with these membranes, may be an important aspect of their possible beneficial effects on human health.--Britton, G. Structure and properties of carotenoids in relation to function.

Effect of ?-carotene, lutein and violaxanthin on structural properties of dipalmitoyl-phosphatidylcholine liposomes as studied by ultrasound absorption technique

The effect of three carotenoid pigments, β-carotene, lutein, and violaxanthin, on structural properties of dipalmitoylphosphatidylcholine liposomes was studied by means of ultrasound absorption technique. It was found that the polar carotenoid-lutein enhances drastically ultrasound absorption related to energy consumption during phase transition of a lipid component. The effect of apolar β-carotene was not so much evident. No differences between the sample and control were found in the case of violaxanthin presence in liposomes. The effect of a polar carotenoid is discussed in terms of the reinforcement of the lipid matrix. Physiological aspects of carotenoid action in membranes are also briefly discussed.

19] Assays for regulation of gap functional communication and connexin expression by carotenoids

Publisher Summary Carotenoids as a group are considered to possess antioxidant properties and a few act as provitamin A sources in mammals. This chapter demonstrates a novel carotenoid action that of upregulation of gap junctional communication (GJC). This action is highly correlated with the chemopreventive properties but not with the provitamin A status or lipid-phase antioxidant potency of a series of dietary carotenoids. The induction of GJC by carotenoids is achieved by increasing the expression of connexin 43 (Cx43), one of a family of genes coding for a structural subunit of the gap junction. The chapter describes the measurement of gap junctional communication at the functional level by means of assays of dye transfer. Because junctions may be in the open or closed state, any observed increased dye transfer can be the result of an increased number of junctions and/or an increased number of open junctions. Assays used to distinguish between these possibilities assays are described in the chapter.

Immunomodulating actions of carotenoids: enhancement of in vivo and in vitro antibody production to T-dependent antigens.

Previously, we demonstrated an enhancement of in vitro antibody (Ab) production in response to T-dependent antigens (TD-Ag) by astaxanthin, a carotenoid without vitamin A activity. The effects of beta-carotene, a carotenoid with vitamin A activity, and lutein, another carotenoid without vitamin A activity, on in vitro Ab production were examined with spleen cells from young and old B6 mice. In addition, the in vivo effects of lutein, astaxanthin, and beta-carotene on Ab production were studied in young and old B6 mice. Lutein, but not beta-carotene, enhanced in vitro Ab production in response to TD-Ags. The depletion of T-helper cells prevented the enhancement of Ab production by lutein and astaxanthin. In vivo Ab production in response to TD-Ag was significantly enhanced by lutein, astaxanthin, and beta-carotene. The numbers of immunoglobulin M- and G-secreting cells also increased in vivo with the administration of these carotenoids when mice were primed with TD-Ags. Antibody production in response to TD-Ags in vivo and in vitro was significantly lower in old than in young B6 mice. Astaxanthin supplements partially restored decreased in vivo Ab production in response to TD-Ags in old B6 mice. Lutein and beta-carotene also enhanced in vivo Ab production in response to TD-Ags in old B6 mice, although to a lesser extent than did astaxanthin. However, none of the carotenoids had an effect on in vivo or in vitro Ab production in response to T-independent antigen. These results indicate significant immunomodulating actions of carotenoids for humoral immune responses to TD-Ags and suggest that carotenoid supplementation may be beneficial in restoring humoral immune responses in older animals.

Molecular actions of carotenoids.

Carotenoids can be attacked enzymatically at almost every position in the molecule. On the other hand, under dark nonoxidative conditions, they can be very stable. Thus, the precise chemical and biological environment is of crucial importance in determining whether, and how, they are transformed. Three important biologically active derivatives of carotenoids, vitamin A, trisporic acid and abscisic acid, all of which serve as hormones in appropriate cells, are, or can be, formed from precursor carotenoids. Highly active forms of all three hormones are 9-cis isomers. In all cases, the products are involved both in light-induced reactions as well as in cellular differentiation, often related to sexual maturation. Each of these hormones is formed by an initial dioxygenase attack on the central conjugated chain of carotenoids followed by a series of specific reactions. Indeed, when various carotenoids of different structure are studied in humans, each shows a characteristic, if not unique, set of metabolites. Thus, generalizations about carotenoid metabolism must be constrained by precise metabolic information about given compounds. In dealing with the manifold biological activities of carotenoids, it is useful to categorize them as functions, actions or associations. In the hope of gaining greater insight into the relationship between carotenoids, health and longevity, these distinctions should be helpful.

Antioxidant action of carotenoids in vitro and in vivo and protection against oxidation of human low-density lipoproteins.

Antioxidant action of carotenoids in vitro and in vivo and protection against oxidation of human low-density lipoproteins.

Cooxidations: significance to carotenoid action in vivo.

Cooxidations: significance to carotenoid action in vivo.

Putative anticarcinogenic actions of carotenoids: nutritional implications.

This review provides an update on nutritional aspects of carotenoids (as distinct from retinoids), with specific relevance to anticarcinogenesis. Critical gaps remain in our knowledge of the nutritional functions of carotenoids despite an overwhelming accumulation of research data in areas tangential to human nutrition. In addition to their roles as precursors of retinol and retinoids, carotenoids have distinct functions of their own in animals and humans. In vitro they are antioxidants with a broad range of potencies. In vivo, they protect porphyrics against sunlight. The evidence for anticarcinogenic actions of beta-carotene in certain specified test situations is persuasive. Nevertheless, despite a large number of studies demonstrating protection by carotenoids, the characteristics that render a given carotenoid effective and the relative efficacy of the individual carotenoids are not known. Moreover, dose-response and pharmacokinetic relationships remain virtually unexplored. Research to uncover mechanisms of protection by carotenoids is, for technical reasons, painfully slow. Epidemiological studies reveal associations but not cause and effect. To explore cause and effect, intervention trials are underway, hampered by the paucity of data regarding optimal choice of carotenoid, dosage, and regimen. The in vitro test systems that would provide this information are not available because the molecular sites relevant to the chemopreventive action of carotenoids are obscure. Each of these problems has a solution, but not a simple one. Until these are resolved, blanket recommendations regarding supplementation will remain problematic. To this point, health authorities have not recommended dietary supplementation with carotenoids. Instead, they recommend increased consumption of yellow and dark green carotenoid-rich vegetables. In the future, an individual at risk for a particular carcinogenic process may be recommended a supplement of the most appropriate anticarcinogen, specific to their individual endowment of genetic and environmental risk factors. This review emphasizes not only what is known but also what is not known. Consequently we identify priorities for research that, if undertaken, will allow such recommendations to be made or discounted with more confidence.

Role of Carotenoids in the Immune Response

The well-established provitamin A activities of certain carotenoids have hampered past research into their possible specific functions. More recently, research interests on carotenoids have been revived, largely because of their anticancer activities. β-Carotene and other carotenoids have been reported to possess immunomodulatory activities in humans and animals. These carotenoids enhance lymphocyte blastogenesis, increase the population of specific lymphocyte subsets, increase lymphocyte cytotoxic activity, and stimulate the production of various cytokines. In addition, carotenoids also stimulate the phagocytic and bacteria-killing ability of blood neutrophils and peritoneal macrophages. The action of these carotenoids is widely accepted to be independent of their provitamin A activity. The immunostimulatory action of carotenoids may be translated into improved health, including mammary and reproductive health in dairy cattle. More studies are needed to establish fully the beneficial effects of supplementation of different carotenoids on the health of dairy cattle. Furthermore, studies on carotenoids other than β-carotene are needed.

Actions of carotenoids in biological systems.

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Studies of immunomodulating actions of carotenoids. II. Astaxanthin enhances in vitro antibody production to T-dependent antigens without facilitating polyclonal B-cell activation.

Previously we have shown that astaxanthin, a carotenoid without provitamin A activity, enhances in vitro antibody (Ab) production to sheep red blood cells in normal B6 mice. In this study, we further attempted to examine the mechanisms of this enhancing action of carotenoids on specific Ab production in vitro in relation to different antigen (Ag) stimuli, cytokine production, and T- and B-cell interactions in both normal and autoimmune strains of mice. When the actions of carotenoids were tested in normal strains of mice, we found that astaxanthin enhanced in vitro Ab production to T cell-dependent Ag, but not to T-independent Ag, and did not augment total immunoglobulin production. Astaxanthin exerted maximum enhancing actions when it was present at the initial period of Ag priming. This action of astaxanthin was abolished when T cells were depleted from spleen cell suspensions and appeared to require direct interactions between T and B cells. The results also indicated that carotenoids may modulate the production of interferon-tau in this assay system. When the actions of carotenoids were tested in autoimmune-prone MRL and NZB mice, the enhancing action of astaxanthin on in vitro Ab production was less significant. Furthermore, carotenoids did not potentiate or augment spontaneous Ab and immunoglobulin production by spleen cells in these strains. Taken together, carotenoids without provitamin A activity may be able to augment in vitro specific Ab production to T cell-dependent Ag partly through affecting the initial stage of Ag presentation without facilitating polyclonal B-cell activation or autoantibody production.

Actions of Carotenoids in Biological Systems

Actions of Carotenoids in Biological Systems

Preventive Action of Carotenoids on the Development of Lymphadenopathy and Proteinuria in MSL-lpr/lprMice

The chemopreventive action of carotenoids on proteinuria and lymphadenopathy were examined in autoimmune-prone MRL-lpr/lpr (MRL/l) mice. They were fed a synthetic full-fed diet (16-18 kcal/mouse/day) with supplementation of beta-carotene or astaxanthin (0.19 mumoles/mouse, 3 times a week), and the development of lymphadenopathy and proteinuria were examined. MRL/l mice fed a full-fed diet without the supplementation of carotenoids or those fed a calorie-restricted (CR) diet (10-11 kcal/mouse/day, 60% calorie intake of full-fed mice) were employed as controls. CR dramatically delayed the development of proteinuria and lymphadenopathy, as reported previously. Carotenoids also significantly delayed the onset of these symptoms in MRL/l mice fed a full-fed diet. Carotenoids were half as effective as CR and astaxanthin, a carotenoid without provitamin A activity, which appeared to exert more significant preventive actions than beta-carotene in delaying the development of these symptoms. Similar chemopreventive actions of carotenoids were also demonstrated in MRL/l mice fed a regular diet (Lab Chow). CR has been shown to augment IL-2 production and to decrease serum prolactin levels in this strain, which may be related to its dramatic preventive action of autoimmunity. However, carotenoids did not affect IL-2 production nor prolactin levels in full-fed MRL/l mice. The chemopreventive actions of carotenoids observed in autoimmune-prone MRL/l mice may be attributed to yet unknown mechanisms, apart from their provitamin A activity or oxygen-quenching activity.