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PubMed2005

Turnover and characterization of UDP-N-acetylglucosaminyl transferase in a stably transfected HeLa cell line.

To estimate the turnover of UDP-N-acetylglucosaminyl transferase (OGT), we exposed stably transfected HeLa cells to tetracycline for 16h to induce OGT gene expression and increase cytosolic enzyme levels. Removal of tetracycline led to a progressive decrease in OGT activity (after a 6h lag period), yielding an estimated OGT half-life of 13h. A similar half-life (12h) was obtained by measuring the loss of biosynthetically labeled OGT ([35S]methionine pulse-chase experiments). Since OGT turnover was relatively slow, it is unlikely that changes in OGT gene expression or protein expression play a role in the short-term regulatory actions mediated by the hexosamine signaling pathway. We also found that the overexpressed 110kDa murine OGT subunit (recombinant enzyme) was enzymatically similar to the endogenous holoenzyme derived from rat brain tissue. Thus, stably transfected HeLa cells provide an abundant source of enzyme that can be used to study the structure, function, and regulation of OGT.

Gene Expression Regulation, Enzymologic↗
PubMed2005

Alterations in the intestinal glycocalyx and bacterial flora in response to oral indomethacin.

Nonsteroidal anti-inflammatory drugs (NSAIDs), used extensively in clinical medicine, tend to cause adverse effects in the gastrointestinal tract. Earlier work has shown that oral administration of indomethacin produced oxidative damage in the small intestine and attenuation of the glycocalyx layer of the mucosa. The present study assessed, in greater detail, the alterations produced in the glycocalyx of rat small intestinal mucosa in response to indomethacin, with specific reference to surfactant-like particles (SLP) and brush border membranes (BBM). Changes in gut flora in response to the drug were also studied, as it has been shown that luminal bacteria play a role in the pathogenesis of NSAID-induced intestinal damage. The levels of sugars such as sialic acid, fucose, hexose and hexosamine were increased in SLP and decreased in the BBM following indomethacin treatment, with the effects being maximal 24h after the administration of the drug. The composition of lipids in the SLP was also found to be altered. There was a significant increase in the number of bacteria in the luminal contents of the small intestine and caecum in these animals, as compared with controls. The number of bacteria adherent to the intestinal mucosa was also significantly higher in the drug-treated group. In vitro studies revealed that there was an increased tendency for bacteria to adhere to SLP isolated from indomethacin-treated rats. These results suggest that alterations in glycosylation of SLP and BBM in response to indomethacin, along with qualitative and quantitative changes in the luminal bacterial flora, may facilitate translocation of bacteria into the mucosa. These changes may contribute to the enteropathy observed as a result of NSAID treatment.

Administration, Oral↗
PubMed2005

Glucosamine-induced phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 is mediated by the protein kinase R-like endoplasmic-reticulum associated kinase.

In diabetic animals, enhanced production of vascular endothelial growth factor is thought to be a major contributor to the development of diabetic retinopathy. In the present study, glucosamine-treated R28 retinal neuronal cells were used as an experimental model system to explore the possible involvement of the hexosamine biosynthetic pathway in the diabetes-induced changes in mRNA translation. Glucosamine treatment enhanced vascular endothelial growth factor production subsequent to changes in phosphorylation of the alpha-subunit of eukaryotic initiation factor 2, with no change in vascular endothelial growth factor mRNA content. Possible mechanisms through which glucosamine might act to increase eukaryotic initiation factor 2alpha phosphorylation include enhanced O-linked glycosylation of protein kinase or phosphatase regulatory proteins and/or induction of oxidative stress. However, increasing global protein O-glycosylation through inhibition of O-beta-N-acetylglucosaminidase did not mimic the effect of glucosamine on eukaryotic initiation factor 2alpha phosphorylation. Likewise, attenuating glucosamine-induced oxidative stress with two different antioxidants did not reduce glucosamine-induced eukaryotic initiation factor 2alpha phosphorylation. Glucosamine treatment was also found to promote eukaryotic initiation factor 2alpha phosphorylation in wild-type mouse embryonic fibroblasts, but not in mouse embryonic fibroblasts lacking the eukaryotic initiation factor 2alpha kinase referred to as RNA-dependent protein kinase-like endoplasmic-reticulum associated kinase, implicating the kinase in the glucosamine-induced increase in eukaryotic initiation factor 2alpha phosphorylation. Overall, the results are consistent with glucosamine causing activation of RNA-dependent protein kinase-like endoplasmic-reticulum associated kinase, which phosphorylates eukaryotic initiation factor 2alpha and consequently upregulates translation of mRNAs encoding specific proteins, such as vascular endothelial growth factor.

Animals↗
PubMed2006

Enzymatic characterization of O-GlcNAcase isoforms using a fluorogenic GlcNAc substrate.

A highly sensitive fluorogenic hexosaminidase substrate, fluorescein di(N-acetyl-beta-D-glucosaminide) (FDGlcNAc), was prepared essentially as described previously [Chem. Pharm. Bull. 1993, 41, 314] with some modifications. The fluorescent analog is a substrate for a number of hexosaminidases but here we have focused on the cytoplasmic O-GlcNAcase isoforms. Kinetic analysis using purified O-GlcNAcase and its splice variant (v-O-GlcNAcase) expressed in Escherichia coli suggests that FDGlcNAc is a much more efficient substrate (Km = 84.9 microM) than the conventional substrate, para-nitrophenyl 2-acetamido-2-deoxy-beta-D-glucopyranoside (pNP-beta-GlcNAc, Km = 1.1 mM) and a previously developed fluorogenic substrate, 4-methylumbelliferyl 2-acetamido-2-deoxy-beta-D-glucopyranoside [MUGlcNAc, Km = 0.43 mM; J. Biol. Chem. 2005, 280, 25313] for O-GlcNAcase. The variant O-GlcNAcase, a protein lacking the C-terminal third of the full-length O-GlcNAcase, exhibited a Km of 2.1 mM with respect to FDGlcNAc. This shorter isoform was not previously thought to exhibit O-GlcNAcase activity based on in vitro studies with pNP-beta-GlcNAc. However, both O-GlcNAcase isoforms reduced O-GlcNAc protein levels extracted from HeLa and HT-29 cells in vitro, indicating that the splice variant is a bona fide O-GlcNAcase. Fluorescein di-N-acetyl-beta-D-galactosaminide (FDGalNAc) is not cleaved by these enzymes, consistent with previous findings that the O-GlcNAcase has substrate specificity toward O-GlcNAc but not O-GalNAc. The enzymatic activity of the shorter isoform of O-GlcNAcase was first detected by using highly sensitive fluorogenic FDGlcNAc substrate. The finding that O-GlcNAcase exists as two distinct isoforms has a number of important implications for the role of O-GlcNAcase in hexosamine signaling.

Acetylglucosaminidase↗
PubMed2005

Biochemical evaluation of the inflammatory changes in cardiac, hepatic and renal tissues of adriamycin-administered rats and the modulatory role of exogenous heparin-derivative treatment.

The aim of the present work is to evaluate the role of a heparin derivative, low molecular weight heparin (LMWH), certoparin on the inflammatory changes in adriamycin (ADR) cytotoxicity on a biochemical basis. Male Wistar rats (140+/-10g) were divided into four groups: untreated control, ADR group (a single dose intravenous injection of 7.5 mg/kg ADR), LMWH control (300 microg/(day rat) s.c. for 1 week) and ADR plus LMWH group (7.5 mg/kg ADR on day 1 of study period followed by LMWH treatment, 300 microg/(day rat) commencing on day 8 and continued for 1 week). At the end of the 2-week experimental period, biochemical assessment of the inflammatory status was carried out in the plasma, cardiac, hepatic and renal tissues. Increased concentrations of plasma C-reactive protein (CRP) and fibrinogen indicated severe inflammation in the ADR cytotoxic rats. These acute-phase inflammatory markers diminished significantly in the LMWH treated group, when compared with the cytotoxic group (p<0.001). Tissue damage was marked by elevated levels of plasma and tissue hexose, hexosamine, hexuronic acid and sialic acid, which were reversed on LMWH administration (p<0.001). The activities of lysosomal enzymes was measured in the experimental groups, and it was observed that the ADR induced rats showed a marked increase in the enzymic activities, while LMWH treated rats revealed normal activities. The present study throws light on the inflammatory changes in the ADR-challenged heart, liver and kidney tissues, and projects the biochemical basis for the anti-inflammatory property of the LMWH, certoparin.

Acute-Phase Reaction↗
PubMed2006

Therapeutic effects of Semecarpus anacardium Linn. nut milk extract on the changes associated with collagen and glycosaminoglycan metabolism in adjuvant arthritic Wistar rats.

The effect of milk extract of Semecarpus anacardium Linn. nut milk extract (SA) was studied to gain some insight into this intriguing disease with reference to collagen metabolism. Arthritis was induced in rats by injecting Freund's complete adjuvant containing 10mg of heat killed mycobacterium tuberculosis in 1 ml paraffin oil (0.1 ml) into the left hind paw of the rat intradermally. After 14 days of induction, SA (150 mg/kg body weight/day) was administered orally by gastric intubations for 14 days. Decreased levels of collagen and glycosaminoglycans (GAGS) components (chondroitin sulphate, heparan sulphate, hyaluronic acid) and increase in the levels of connective tissue degrading lysosomal glycohydrolases such as acid phosphatase, beta-glucuronidase, beta-N-acetyl glucosaminidase and cathepsin-D observed in arthritic animals were reverted back to near normal levels upon treatment with SA. The drug effectively regulated the uriniray markers of collagen metabolism namely hexosamine, hexuronic acid, hydroxyproline and total GAGS. Electron microscopic studies also revealed the protective effect of SA. Hence, it can be suggested that SA very effectively regulate the collagen metabolism that derange during arthritic condition.

Adjuvants, Immunologic↗
PubMed2006

Modulatory efficacy of green tea polyphenols on glycoconjugates and immunological markers in 4-Nitroquinoline 1-oxide-induced oral carcinogenesis-A therapeutic approach.

Green tea polyphenols (GTP) has been used as a chemopreventive agent world wide against chemically induced cancer. The present study is aimed to understand the therapeutic action of GTP on glycoconjugates and immunological markers in 4-Nitroquinoline 1-oxide (4-NQO)-induced oral cancer over a period of 30 days at 200mg/kg, p.o., Oral cancer was induced by painting 4-NQO for 8 weeks followed by administration of GTP after 22 weeks, for 30 days. Glycoconjugates such as hexose, hexosamine, sialicacid, fucose and mucoprotein were analysed. Expression of glycoconjugates was examined through histology and SDS-PAGE. Immunological markers such as circulating immune complex and mast cell density were studied. Oral cancer-induced animals showed a significant increase in levels of glycoconjugates and its expression, similar to that observed for immunological markers. Treatment with GTP altered the expression of glycoconjugates as well as immunological markers. The results suggest that GTP modulates both the expression of glycoconjugates and immunological markers resulting in regression of oral cancer.

4-Nitroquinoline-1-oxide↗
PubMed2005

Glyco-oxidation in diabetes and related diseases.

BACKGROUND: Recent evidence has shown that hyperglycemia is able to cause increased production of superoxide on the mitochondrial transport chain, and that this is the key event which activates some events such as increased AGE formation, increased hexosamine and polyol flux, and activation of PKC, all believed to be important for the development of the chronic complications of diabetes, aging and uremia. In this context, non-enzymatic protein glyco-oxidation leads to the formation of a series of products whose intra- and extra-cellular accumulation is of key importance in the pathogenesis of these chronic diseases. METHODS: Various spectrometric approaches, such as matrix-assisted laser desorption ionisation (MALDI), and liquid chromatography-electrospray ionisation (ESI) were used. RESULTS AND CONCLUSIONS: The latest mass spectrometric approaches have shown their power in proteomics, and we report here some applications of this technique in the study of in vitro and in vivo non-enzymatic protein glyco-oxidation.

Diabetes Mellitus↗
PubMed2026

Genome-wide CRISPR screens map synthetic lethal interactions across recurrent cancer driver alterations.

Synthetic lethality (SL) provides a treatment paradigm for targeting cancer with alterations in driver genes that are not conventionally druggable, including tumor suppressor genes. We execute a series of genome-wide CRISPR screens using functionally validated isogenic cell lines and conduct a large-scale SL analysis using data from the cancer dependency map (DepMap). We chart SL interactions across 15 driver alterations: FBXW7, CCNE1, CDK12, ARID1A, KMT2D, DNMT3A, TET2, KEAP1, STK11, IDH1, SF3B1, SRSF2, U2AF1, chromosome 18q loss, and chromosome 13q loss. We show validation of several SL interactions, including ARID1A and the hexosamine biosynthetic pathway aminotransferase GFPT1, STK11 with CAMK protein kinase MARK2, FBXW7 and the CDK1 regulatory kinase PKMYT1, and CCNE1 amplification and the anaphase-promoting complex or cyclosome (APC/C). In summary, this study offers a rich resource of genetic interactions across cancer drivers enabling the discovery of biological insights and drug targets for future therapeutic development.

CP: cancer↗
PubMed2005

Analysis of sialyl oligosaccharides by high-performance liquid chromatography-electrospray ionisation-mass spectrometry with differentiation of alpha2-3 and alpha2-6 sialyl linkages.

A method for analysing sialyl oligosaccharides from bovine colostrum using high-performance liquid chromatography-electrospray ionisation-mass spectrometry (HPLC-ESI-MS) is described. Under positive ionisation mode, mass spectra of alpha2-3 and alpha2-6 linkages were different, and the former produced a prominent B2 (or B3 in disialyl lactose) mass fragment. This fragment was absent from mass spectra with alpha2-6 linkages. Two sialyl oligosaccharides, which have not been reported previously, were tentatively identified. One comprises a N-acetyl neuraminic acid (Neu5Ac), two hexoses (Hex), and one N-acetyl hexosamine (HexNAc) residue ((Neu5Ac)1 (Hex)2 (HexNAc)1), and the other comprises one Neu5Ac and one Hex residue ((Neu5Ac)1(Hex)1).

Carbohydrate Sequence↗
PubMed2005

Mechanisms of insulin resistance caused by nutrient toxicity.

Insulin resistance, the impaired action of insulin, has been linked to many important consequences, including Type 2 diabetes, hypertension, dyslipidemia, acanthosis nigricans and polycystic ovarian syndrome. Although there are some genetic causes for insulin resistance, the most common cause is an excess of nutrition a condition called "Nutrient Toxicity". Both excess glucose and excess fat can cause insulin resistance in muscle and fat tissues and excess fat can cause insulin resistance in the liver. High fat feeding and fat infusion rapidly lead to the development of insulin resistance caused by impairment in glucose transport. Other studies have shown defects in insulin signaling possibly secondary to activation of Protein Kinase C resulting from the accumulation of active fatty acyl CoA's. Glucose toxicity has been studied both in vivo and in vitro. In vivo it has been shown that rats over-expressing the gluconeogenic enzyme Phosphoenol Pyruvate Carboxykinase (PEPCK) develop insulin resistance in fat and muscle tissues and some features of the metabolic syndrome including mild obesity and dyslipidemia. Excess glucose entry in fat cells results in increased flux through the hexosamine biosynthesis pathway leading to activation of protein kinase C and impairment of glucose transport. Obesity resulting from excess nutrient intake can also cause insulin resistance by an increase in the production of agents that impair insulin action such as TNFalpha and resistin and a decrease in the production of an insulin sensitizing compound adiponectin. Both glucose and free fatty acids acutely stimulate insulin secretion but chronic exposure to high levels of either nutrient leads to impairment of beta cell function. The combination of insulin resistance and beta cell failure leads to diabetes. Nutrient toxicity is thus the driving cause of the diabetes epidemic that is being recorded around the world.

Journal Article↗
PubMed2006

Favourable modulation of the inflammatory changes in hypercholesterolemic atherogenesis by a low-molecular-weight heparin derivative.

BACKGROUND: In the hypercholesterolemic state, the net result of combined oxidative and nitrosative stress is a pro-inflammatory phenotype that is manifested as increased adhesion molecule expression, enhanced leucocyte trafficking, and increased vascular permeability. The present work explores the inflammatory aspects of hypercholesterolemic atherogenesis, and also evaluates the role of a low-molecular-weight heparin derivative (LMWH), Certoparin, on a biochemical basis. METHODS AND RESULTS: Two groups of male Wistar rats were fed an atherogenic diet (normal rat chow plus 4% cholesterol, 1% cholic acid and 0.5% thiouracil-CCT diet) for 2 weeks. While one was left untreated, the other was administered LMWH (300 microg/day/rat commencing on day 8 and continued for a week). Increased concentrations of plasma C-reactive protein and fibrinogen and cardiac TNF-alpha indicated severe inflammation in the atherogenic diet fed rats. In comparison, these biochemical indices of inflammation diminished significantly in the LMWH treated group (p < 0.001). Significant depletion of thiols, along with accentuated activities of the glutathione metabolising was observed in the cardiac and hepatic tissues of the untreated atherogenic rats, indicating heightened oxidative response. Tissue damage was marked by elevated levels of plasma and tissue hexose, hexosamine, hexuronic acid and sialic acid, which were reversed towards normalcy on LMWH administration. The activities of lysosomal enzymes (N-acetyl glucosaminidase, beta-glucuronidase, beta-galactosaminidase and cathepsin-D) showed a marked increase in the CCT-diet fed rats, while LMWH treated rats showed normal activities (p < 0.001). The osmotic fragility test revealed that the untreated hyperlipidemic rat erythrocytes were significantly fragile at high salt concentrations, while the response was normalized in the LMWH treated group (p < 0.05). Further, hypercholesterolemia induced downregulation of physiological nitric oxide levels was corrected upon treatment with heparin-derivative. CONCLUSION: The results of this work highlight the inflammatory changes in atherogenic conditions and that the low-molecular-weight heparin derivative affords substantial protection.

Animals↗
PubMed2006

Characterization of glutamine: fructose-6-phosphate aminotransferase from the ixodid tick, Haemaphysalis longicornis, and its critical role in host blood feeding.

Glutamine: fructose-6-phosphate aminotransferase (GFAT, EC2.6.1.16) is the first, and rate-limiting, enzyme in the hexosamine biosynthetic pathway, and is involved in the regulation of chitin biosynthesis and glycosylation of proteins. We report here the molecular characterization and potential functions of a novel GFAT (HlGFAT) from the ixodid tick Haemaphysalis longicornis. HlGFAT consists of 696 amino acids, possesses a class II glutamine aminotransferase domain and two sugar isomerase motifs, and has a close phylogenetic relationship to insect GFAT. HlGFAT was expressed at all stages of development and in multiple organs. The transcription levels in the cuticle and midgut were enhanced significantly by blood feeding during the first 3 days and decreased on the fifth day, while those in salivary glands maintained almost the same level during the first 3 days, and decreased to a rather low level at 5 days postinfestation. Endogenous HlGFAT was identified at all developmental stages and in multiple organs, such as epidermis, midgut epithelium, salivary gland, ovary, Malpigian's tubule and trachea. It was identified as a protein of 78.4 kDa using Western blot analysis. Following RNA interference of HlGFAT, engorgement by adult females was reduced significantly. One of the potential mechanisms for this effect may be that the inhibition of HlGFAT limits chitin biosynthesis, so disrupting cuticle growth and possibly peritrophic matrix formation during blood feeding.

Animals↗
PubMed2004

Inhibitory effect of a polysaccharide from Tinospora cordifolia on experimental metastasis.

Administration of the polysaccharide fraction from Tinospora cordifolia was found to be very effective in reducing the metastatic potential of B16F-10 melanoma cells. There was a 72% inhibition in the metastases formation in the lungs of syngeneic C57BL/6 mice, when the drug was administered simultaneously with tumour challenge. Biochemical parameters such as lung collagen hydroxyproline, hexosamines and uronic acids that are markers of neoplastic development were reduced significantly (P<0.001) in the treated animals compared with the untreated control animals. The treatment could also reduce serum gamma-glutamyltranspeptidase (gamma-GT) and sialic acid levels as compared to the control animals.

Animals↗
PubMed2005

Advances in understanding the molecular causes of diabetes-induced birth defects.

OBJECTIVE: To review the current understanding of the molecular causes of birth defects resulting from diabetic pregnancy, with a focus on neural tube defects. METHODS: A mouse model of diabetic pregnancy is described, in which embryo gene expression associated with neural tube defects is examined. Chemical, physiologic, or genetic manipulations are employed to elucidate critical pathways affected by increased glucose metabolism, and how abnormal gene expression disrupts neural tube closure. RESULTS: Increased glucose delivery to embryos, or activation of pathways that are stimulated by high glucose, such as the hexosamine biosynthetic pathway or hypoxia, increase oxidative stress in embryos, inhibit expression of Pax3, a gene that encodes a transcription factor that is required for neural tube closure, and increase neural tube defects. Conversely, blocking these pathways, or providing the antioxidants, reduced glutathione or vitamin E, suppress the adverse effects of excess glucose. Pax3 decreases steady-state levels of the p53 tumor-suppressor protein, such that when Pax3 is deficient, p53 protein increases, leading to increased neuroepithelial apoptosis prior to completion of neural tube closure. Embryos that lack both functional Pax3 protein and p53 do not display neuroepithelial apoptosis or neural tube defects. CONCLUSIONS: Excess glucose metabolism by embryos resulting from maternal hyperglycemia disturbs a complex network of biochemical pathways, leading to oxidative stress. Oxidative stress inhibits expression of genes, such as Pax3, which control essential developmental processes. Pax3 protein is required during neural tube development to suppress p53-dependent cell death and consequent abortion of neural tube closure, but is not required to control expression of genes that direct neural tube closure. Impaired embryo gene expression resulting from oxidative stress, and consequent apoptosis or disturbed organogenesis, may be a general mechanism to explain diabetic embryopathy.

Animals↗
PubMed2004

Inhibitory effect of Boerhaavia diffusa on experimental metastasis by B16F10 melanoma in C57BL/6 mice.

Administration of the aqueous methanol (3:7) extract of B.diffusa was found to be effective in reducing the metastases formation by B16F10 melanoma cells. Prophylactic administration of the extract (0.5 mg/dose) inhibited the metastases formation by about 95% as compared to untreated control animals. There was 87% of inhibition in the lung metastases formation in syngenic C57BL/6 mice, when the extract was administered simultaneously with tumour challenge. Biochemical parameters such as lung collagen hydroxyproline, hexosamines and uronic acid levels were also reduced significantly (P < 0.001) in the treated animals. Levels of serum sialic acids and gamma-glutamyltranspeptidase that are markers of neoplastic proliferation were also reduced in the tumour plus extract treated animals. More over treatment with the extract enhanced the survival of the animals more than double that of untreated control animals. When a non-toxic concentration of the extract was treated directly to the B16F10 cells in vitro, it inhibited the cell proliferation as estimated by the 3H - thymidine uptake assay. From the Zymogram analysis using culture supernatant from the extract treated cells it became evident that the components of the extract inhibited the expression or activity of gelatinases A and B (MMP-2 and MMP-9). Since the MMPs are intimately associated with cell invasion and angiogenesis, inhibition of these functions along with the anti-proliferative activity (cytostatic) may be contributing to the antimetastatic property shown by B. diffusa.

Animals↗
PubMed2004

Effect of glucosamine on apolipoprotein AI mRNA stabilization and expression in HepG2 cells.

Previously published studies suggest that an alteration in hexosamine flux induces a state of insulin resistance in muscle, liver, and other cell types. Glucosamine also alters the expression of several genes through an effect on transcription factors such as Sp1. Since the anti-atherogenic protein apolipoprotein AI (apoAI) is positively regulated by insulin, at least partly through its effect on Sp1, we investigated the effect of glucosamine on apoAI gene expression in the hepatocyte cell line, HepG2. By 24 hours of treatment with 0.1, 1, or 3 mmol/L glucosamine, the amount of apoAI protein secreted into the culture media increased 1.8-fold, 5.5-fold, and 2.3-fold, respectively. The decline in apoAI secretion at the highest glucosamine levels may be due to toxicity since the percentage of cells able to exclude trypan blue was lower in this group than in control cells (98.5% +/- 1.5% in control cells v 89.2% +/- 2.1% in cells treated with 3 mmol/L glucosamine, P <.01). ApoAI mRNA levels increased 2.4-fold in hepatocytes treated with 1 mmol/L glucosamine for 24 hours (1,158.1 +/- 78.8 v 482.2 +/- 24.3 arbitrary integrator units [AIU], P <.02), suggesting that the increase in apoAI protein secretion was due, at least partly, to an increase in apoAI mRNA levels. However, glucosamine had no effect on apoAI gene transcription rate as measured by nuclear runoff analysis (3,155 +/- 46.0 in control cells v 3,181 +/- 30.0 AIU in glucosamine-treated cells). Similarly, apoAI promoter activity measured in HepG2 cell transfected with an apoAI reporter plasmid containing the full-length apoAI promoter including an insulin-responsive Sp1 binding site did not change with glucosamine addition. In this assay, the chloramphenicol acetyltransferase (CAT) activity was 12.4% +/- 3.1%, 10.1% +/- 2.4%, 9.8% +/- 2.0%, 9.7% +/- 2.2%, and 11.9% +/- 2.9% in cells treated with 0, 0.03, 0.1, 0.3, and 1 mmol/L glucosamine, respectively. The apoAI mRNA turnover studies showed that 1 mmol/L glucosamine treatment of HepG2 cells was associated with increased apoAI mRNA half-life, from 7.6 to 16.6 hours. These findings suggest that increases in apoAI gene expression by glucosamine occur primarily through stabilizing apoAI mRNA.

Apolipoprotein A-I↗
PubMed2004

The anti-gastric ulcer effect of Gynostemma pentaphyllum Makino.

Gynostemma pentaphyllum is an oriental medicinal herb reputed to have broad-spectrum activities. The plant's principal saponin components are structurally similar to those found in ginseng plants and this similarity is assumed to be responsible for the claimed activities. The present study was undertaken to evaluate a G. pentaphyllum butanol fraction (GPB) for its anti-gastric ulcer activity using experimental models. Oral administration of the GPB at 200 and 400 mg/kg body wt. significantly inhibited gastric ulcer formation induced by indomethacin, HCl/EtOH and water-immersion restraint stress in rats. In pylorus-ligated rats, pretreatment with the GPB had no effect on gastric volume, pH or acidity output, thus indicating a lack of anti-secretory effect. In ethanol-induced ulcerated rats, gastric wall mucus and hexosamine content were markedly preserved by GPB pretreatment. The findings indicate that the butanol fraction of G. pentaphyllum possesses gastroprotective potential related to the preservation of gastric mucus synthesis and secretion.

Administration, Oral↗