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P Netter

Publications and source records attributed to P Netter.

At least 19 recordsLinked to original sources
PubMed2006

Agonists of peroxisome proliferators-activated receptors (PPAR) alpha, beta/delta or gamma reduce transforming growth factor (TGF)-beta-induced proteoglycans' production in chondrocytes.

OBJECTIVE: To investigate the potency of selective agonists of peroxisome proliferators-activated receptors' (PPAR) isotypes (alpha, beta/delta or gamma) to modulate the stimulating effect of transforming growth factor-beta1 (TGF-beta1) on proteoglycans' (PGs) synthesis in chondrocytes. METHOD: Rat chondrocytes embedded in alginate beads and cultured under low serum conditions were exposed to TGF-beta1 (10 ng/ml), alone or in combination with the following agonists: Wy14643 for PPARalpha, GW501516 for PPARbeta/delta, rosiglitazone (ROSI) for PPARgamma, in the presence or absence of PPAR antagonists (GW6471 for PPARalpha, GW9662 for PPARgamma). PGs' synthesis was evaluated by radiolabelled sulphate incorporation and glycosaminoglycans' (GAGs) content by Alcian blue staining of beads and colorimetric 1.9 dimethyl-methylene blue assay after beads' solubilization. Phosphorylation of Extracellular Signal-related Kinase1/2 (ERK1/2), Smad2/3 and p38-MAPK was assessed by Western Blot and production of prostaglandin E2 (PGE2) by Enzyme immuno-assay (EIA). Levels of mRNA for PPAR target genes [acyl-CoA oxidase (ACO) for PPARalpha; mitochondrial carnitin palmitoyl transferase-1 (CPT-1) for PPARbeta/delta and adiponectin for PPARgamma], aggrecan, TGF-beta1 and genes controlling GAGs' side chains' synthesis were quantified by real time polymerase chain reaction and normalized over RP29 housekeeping gene. RESULTS: ACO was selectively up-regulated by 100 microM of Wy14643, CPT-1 by 100 nM of GW501516 and adiponectin by 10 microM of ROSI without cell toxicity. TGF-beta1 increased PGs' synthesis by four-fold, GAGs' content and deposition by 3.5-fold and six-fold, respectively, while inducing aggrecan expression around 10-fold without modifying mRNA levels of GAGs' controlling enzymes. PPAR agonists inhibited the stimulating effect of TGF-beta1 by 24-44% on PGs' synthesis and over 75% on aggrecan, GAGs' content and deposition with the following rank order of potency: ROSI>GW501516> or =Wy14643. TGF-beta1-induced phosphorylation of Smad2/3 and ERK1/2 was reduced by ROSI over GW501516 but not by Wy14643 whereas stimulated PGE2 production was inhibited by Wy14643 over GW501516 but not by ROSI. The effect of PPAR agonists on PPAR target genes and TGF-beta1-induced aggrecan expression was reversed selectively by PPAR antagonists. CONCLUSION: In chondrocytes' beads, PPAR agonists reduced the stimulating effect of TGF-beta1 on PGs by inhibiting TGF-beta1-induced aggrecan expression in an isotype-selective manner. Thus, PPAR agonists could be deleterious in situation of cartilage repair although being protective in situation of cartilage degradation.

Animals↗
PubMed2006

EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the diagnosis of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert, representing 13 European countries. Ten key propositions regarding diagnosis were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Wherever possible the sensitivity, specificity, likelihood ratio (LR), and incremental cost-effectiveness ratio were calculated for diagnostic tests. Relative risk and odds ratios were estimated for risk factors and co-morbidities associated with gout. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 10 key propositions were generated though three Delphi rounds including diagnostic topics in clinical manifestations, urate crystal identification, biochemical tests, radiographs, and risk factors/co-morbidities. Urate crystal identification varies according to symptoms and observer skill but is very likely to be positive in symptomatic gout (LR = 567 (95% confidence interval (CI), 35.5 to 9053)). Classic podagra and presence of tophi have the highest clinical diagnostic value for gout (LR = 30.64 (95% CI, 20.51 to 45.77), and LR = 39.95 (21.06 to 75.79), respectively). Hyperuricaemia is a major risk factor for gout and may be a useful diagnostic marker when defined by the normal range of the local population (LR = 9.74 (7.45 to 12.72)), although some gouty patients may have normal serum uric acid concentrations at the time of investigation. Radiographs have little role in diagnosis, though in late or severe gout radiographic changes of asymmetrical swelling (LR = 4.13 (2.97 to 5.74)) and subcortical cysts without erosion (LR = 6.39 (3.00 to 13.57)) may be useful to differentiate chronic gout from other joint conditions. In addition, risk factors (sex, diuretics, purine-rich foods, alcohol, lead) and co-morbidities (cardiovascular diseases, hypertension, diabetes, obesity, and chronic renal failure) are associated with gout. SOR for each proposition varied according to both the research evidence and expert opinion. CONCLUSIONS: 10 key recommendations for diagnosis of gout were developed using a combination of research based evidence and expert consensus. The evidence for diagnostic tests, risk factors, and co-morbidities was evaluated and the strength of recommendation was provided.

Advisory Committees↗
PubMed2006

EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the management of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert representing 13 European countries. Key propositions on management were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Where possible, effect size (ES), number needed to treat, relative risk, odds ratio, and incremental cost-effectiveness ratio were calculated. The quality of evidence was categorised according to the level of evidence. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 12 key propositions were generated after three Delphi rounds. Propositions included both non-pharmacological and pharmacological treatments and addressed symptomatic control of acute gout, urate lowering therapy (ULT), and prophylaxis of acute attacks. The importance of patient education, modification of adverse lifestyle (weight loss if obese; reduced alcohol consumption; low animal purine diet) and treatment of associated comorbidity and risk factors were emphasised. Recommended drugs for acute attacks were oral non-steroidal anti-inflammatory drugs (NSAIDs), oral colchicine (ES = 0.87 (95% confidence interval, 0.25 to 1.50)), or joint aspiration and injection of corticosteroid. ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout. Allopurinol was confirmed as effective long term ULT (ES = 1.39 (0.78 to 2.01)). If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, allopurinol desensitisation, or a uricosuric. The uricosuric benzbromarone is more effective than allopurinol (ES = 1.50 (0.76 to 2.24)) and can be used in patients with mild to moderate renal insufficiency but may be hepatotoxic. When gout is associated with the use of diuretics, the diuretic should be stopped if possible. For prophylaxis against acute attacks, either colchicine 0.5-1 mg daily or an NSAID (with gastroprotection if indicated) are recommended. CONCLUSIONS: 12 key recommendations for management of gout were developed, using a combination of research based evidence and expert consensus. The evidence was evaluated and the SOR provided for each proposition.

Acute Disease↗
PubMed2006

Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production.

OBJECTIVE: To analyze the distribution of leptin, adiponectin and resistin between paired serum and synovial fluid (SF) samples of patients with osteoarthritis (OA) and to determine the potential sources of these adipokines in the joint. The active free form of leptin was also examined by evaluating the level of the soluble leptin receptor (sOb-R). METHODS: Levels of adipokines and sOb-R were measured by a sandwich enzyme-linked immunosorbent assay in serum and SF collected from OA patients. The levels of adipokines were also determined in conditioned media from cultured joint tissues (synovium, infrapatellar fat pad, meniscus, osteophyte, cartilage and bone). RESULTS: The adipokines exhibited different patterns of distribution between the joint and the circulating compartment. Serum levels of resistin and adiponectin exceeded those in the paired SF. Conversely, leptin SF concentrations were similar or higher than those measured in serum counterparts. Leptin and adiponectin in SF may derive from each joint tissue examined, whereas resistin was not detected in conditioned media of cultured explants. Synovium and infrapatellar fat pad were the major sources of adipokines, but osteophytes released also large amounts of leptin. The sOb-R deficiency found in SF further increased the difference in the bioactive leptin levels between serum and SF. A gender-specific difference was observed with women exhibiting the highest level of free leptin in the joint. CONCLUSION: These data demonstrated that adipokines serum levels are not predictive values for SF determination. The joint cavity is a special space where each adipokine undergoes specific regulatory pathways, strengthening the hypothesis that adipokines may have local effects in the joint and may account for the high prevalence of OA in women.

Adiponectin↗
PubMed2006

Role of the carboxyl terminal stop transfer sequence of UGT1A6 membrane protein in ER targeting and translocation of upstream lumenal domain.

We investigated the role of the stop transfer sequence of human UGT1A6 in ER assembly and enzyme activity. We found that this sequence was able to address and translocate the upstream lumenal domain into microsomal membranes in vitro co- and posttranslationally. The signal activity of this sequence was further demonstrated in HeLa cells by its ability to target and maintain the CD4 protein deleted from both the N-terminal signal peptide and C-terminal transmembrane domain into the ER. We showed that total or partial deletion of the stop transfer sequence of UGT1A6 severely impaired enzyme activity highlighting its importance in both membrane assembly and function.

5' Flanking Region↗
PubMed2006

Dopamine challenge tests as an indicator of psychological traits.

After discussing some introductory considerations about the value of challenge tests in general for discriminating personality dimensions which are considered extrapolations of psychopathological diseases, the present paper outlines the matter of responsivity to agonistic and antagonistic dopaminergic drugs or drugs of different mechanisms of action in the dopaminergic system, and elucidates that different hormones elicited by dopaminergic substances (prolactin, growth hormone) may indicate personality related differences in susceptibility of different brain areas. A further point was to demonstrate not only the well known relationship of dopaminergic hyperactivity with reward seeking and motivational factors associated with extraversion and novelty seeking, but also the relationship of dopaminergic hypofunction with the personality dimension of depression which had already been reported in studies on animals and psychiatric patients. A final point was to demonstrate that besides size of hormone responses additional parameters like time of response onset and initial prolactin increase can be used as biochemical indicators for identifying certain personality types, like highly depressive neurotic persons characterized by lower and later dopamine responses as compared to low depressives, and extraverted sensation-seeking types responding by an initial prolactin peak as opposed to low sensation seekers.

Animals↗
PubMed2006

Cell and tissue engineering and clinical applications: an overview.

Most human tissues do not regenerate spontaneously; this is why cell therapies and tissue engineering are promising alternatives. The principle is simple: cells are collected in a patient and introduced in the damaged tissue or in a tridimentional porous support and harvested in a bioreactor in which the physico-chemical and mechanical parameters are controlled. Once the tissues (or the cells) are mature they may be implanted. In parallel, the development of biotherapies with stem cells is a field of research in turmoil given the hopes for clinical applications that it brings up. Embryonic stem cells are potentially more interesting since they are totipotent, but they can only be obtained at the very early stages of the embryo. The potential of adult stem cells is limited but isolating them induces no ethical problem and it has been known for more than 40 years that bone marrow does possess the regenerating functions of blood cells. Finally, the properties of foetal stem cells (blood cells from the umbilical cord) are forerunners of the haematopoietic system but the ability of these cells to participate to the formation of other tissues is more problematic. Another field for therapeutic research is that of dendritic cells, antigen presenting cells. Their efficiency in cell therapy relies on the initiation of specific immune responses. They represent a promising tool in the development of a protective immune response against antigens which the host is usually unable to generate an efficient response (melanomas, breast against cancer, prostate cancer, ..). Finally, gene therapy, has been nourishing high hopes but few clinical applications can be envisaged in the short term, although potential applications are multiple (haemophilia, myopathies, ..). A large number of clinical areas stand as candidates for clinical applications: leukaemia and cancers, cardiac insufficiency and vascular diseases, cartilage and bone repair, ligaments and tendons, liver diseases, ophthalmology, diabetes, neurological diseases (Parkinson, Huntington disease, ..), .. Various aspects of this new regenerative therapeutic medicine are developed in this work.

Animals↗
PubMed2005

Induction of UGT1A6 isoform by inflammatory conditions in rat astrocytes.

Alteration of drug metabolism under diseased conditions is of clinical importance. We have investigated the effects of inflammatory conditions on phase II drug-metabolizing enzyme activity in rat cultured astrocytes. Lipopolysaccharide (LPS) treatment was used to promote inflammatory conditions. Thus, we reported that LPS initiates an inflammatory response, which is mediated by pro-inflammatory mediators and free radical generation. An increase in astrocyte glucuronidation activity was observed after a 48-h LPS treatment. This increase in glucuronidation activity was associated with an up-regulation of the UGT1A6 isoform mRNA level as shown by RT-PCR and gene reporter assay. Moreover, this endotoxin-induced increase in UGT1A6 expression level was blocked by actinomycin D and cycloheximide, indicating the requirement for RNA and protein synthesis. The UGT1A6 expression enhancement could be prevented by anti-inflammatory drugs (dexamethasone and NS398) or nitric oxide synthase inhibitors (L-NAME and L-NMMA). Moreover, gel shift assay revealed increased activator protein-1 (AP-1) binding activity after LPS treatment. We propose, based on the data presented, that the action of LPS to induce UGT1A6 isoform up-regulation may be mediated by pro-inflammatory mediator accumulation, and AP-1 binding activity increase.

Animals↗
PubMed2005

Analysis of neomycin sulfate and framycetin sulfate by high-performance liquid chromatography using evaporative light scattering detection.

A rapid and simple method for the determination of main components and related substances of both neomycin sulfate and framycetin sulfate by HPLC and evaporative light scattering detection (ELSD) is described. The method was also used to determine the neomycin B and the sample sulfate content. Detection and quantitation of aminoglycoside antibiotics are problematic because of the lack of UV absorbing chromophore. The use of a universal detector avoids the need for sample derivatization or use of specific detector based on pulsed amperometry described to be difficult in routine assays. Separation was performed with a Polaris C18 150 mm x 4.6 mm i.d., 3 microm reversed-phase column with a solution of 170mM trifluoroacetic acid (TFA) mobile phase at a flow rate of 0.2 mL/min. The chromatographic parameters were optimized with the help of experimental design software. Mass spectrometry (MS) was employed to confirm the ELSD profile. The final method was validated using methodology described by the International Conference of Harmonization in the field of Active Pharmaceutical Ingredients. Commercial samples of different sources were analyzed and results were in good agreement with specifications of the European Pharmacopoeia.

Anti-Bacterial Agents↗
PubMed2005

The effect of alginate, hyaluronate and hyaluronate derivatives biomaterials on synthesis of non-articular chondrocyte extracellular matrix.

Cartilage engineering consists of re-constructing functional cartilage by seeding chondrocytes in suitable biomaterials in vitro. The characteristics of neocartilage differ upon the type of biomaterial chosen. This study aims at determining the appropriate scaffold material for articular cartilage reconstruction using non articular chondrocytes harvested from rat sternum. For this purpose, the use of polysaccharide hydrogels such as alginate (AA) and hyaluronic acid (HA) was investigated. Several ratios of AA/HA were used as well as three derivatives obtained by chemical modification of HA (HA-C18, HA-C12(2.3), HA-C12(2.5)-TEG0.5). Sternal chondrocytes were successfully cultured in 3D alginate and alginate/HA scaffolds. HA retention in alginate beads was found to be higher in beads seeded with cells than in beads without cells. HA-C18 improved HA retention in beads but inhibited the chondrocyte synthesis process. Cell proliferation and metabolism were enhanced in all biomaterials when beads were mechanically agitated. Preliminary results have shown that the chondrocyte neo-synthesised matrix had acquired articular characteristics after 21 days culture.

Alginates↗
PubMed2005

[Is leptin the missing link between osteoarthritis and obesity?].

The contribution of leptin, as a possible link between osteoarthritis (OA) and obesity, was studied in cartilage and synovial fluid samples obtained from osteoarthritic patients. Its effect on cartilage was evaluated in rats after intraarticular injections of leptin. Leptin levels were measured in the synovial fluid samples by enzyme linked immunosorbent assay; leptin concentrations were correlated with the body mass index. Leptin was strongly expressed in osteophytes and OA cartilage, while, in normal cartilage, few chondrocytes produced leptin. The level of leptin expression was related to the grade of cartilage destruction and was in good relation with those of growth factors as IGF1 and TGFb. Studies in rats showed that intraarticular leptin injection stimulated anabolic functions of chondrocytes and induced the synthesis of leptin, IGF1 and TGFB in cartilage at both the chondrocytes and induced the synthesis of leptin, IGF1 and TGFB in cartilage at both the mRNA and protein levels. In conclusion, leptin may be a link between osteoarthritis and obesity, and may play a key role in cartilage metabolism. Leptin may contribute to the pathophysiology of OA.

Animals↗
PubMed2005

[Not Available].

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Journal Article↗
PubMed2005

Two types of aggression are differentially related to serotonergic activity and the A779C TPH polymorphism.

The authors investigated whether different types of aggression relate to the A779C tryptophan hydroxylase (TPH) polymorphism and to serotonergic activity in volunteers. A factor analysis of the Buss-Durkee Hostility Inventory yielded 2 factors representing Neurotic Hostility (NH) and Aggressive Hostility (AH). The authors used a neuroendocrine challenge with Citalopram in 48 volunteers and increased cortisol concentrations only in those with high levels of AH. Finally, an association study with 58 volunteers revealed that the A779C TPH polymorphism significantly relates to AH, with the highest aggression levels for the genotype AA and the lowest aggression levels for the genotype CC, but not to NH. Results are discussed with respect to inconsistent findings in the literature, which may be explained by this distinction of types of aggression.

Adult↗
PubMed2004

Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: a strategy to promote cartilage repair.

Osteoarthritis is a degenerative joint disease characterized by a progressive loss of articular cartilage components, mainly proteoglycans (PGs), leading to destruction of the tissue. We investigate a therapeutic strategy based on stimulation of PG synthesis by gene transfer of the glycosaminoglycan (GAG)-synthesizing enzyme, beta1,3-glucuronosyltransferase-I (GlcAT-I) to promote cartilage repair. We previously reported that IL-1beta down-regulated the expression and activity of GlcAT-I in primary rat chondrocytes. Here, by using antisense oligonucleotides, we demonstrate that GlcAT-I inhibition impaired PG synthesis and deposition in articular cartilage explants, emphasizing the crucial role of this enzyme in PG anabolism. Thus, primary chondrocytes and cartilage explants were engineered by lipid-mediated gene delivery to efficiently overexpress a human GlcAT-I cDNA. Interestingly, GlcAT-I overexpression significantly enhanced GAG synthesis and deposition as evidenced by (35)S-sulfate incorporation, histology, estimation of GAG content, and fluorophore-assisted carbohydrate electrophoresis analysis. Metabolic labeling and Western blot analyses further suggested that GlcAT-I expression led to an increase in the abundance rather than in the length of GAG chains. Importantly, GlcAT-I delivery was able to overcome IL-1beta-induced PG depletion and maintain the anabolic activity of chondrocytes. Moreover, GlcAT-I also restored PG synthesis to a normal level in cartilage explants previously depleted from endogenous PGs by IL-1beta-treatment. In concert, our investigations strongly indicated that GlcAT-I was able to control and reverse articular cartilage defects in terms of PG anabolism and GAG content associated with IL-1beta. This study provides a basis for a gene therapy approach to promote cartilage repair in degenerative joint diseases.

Animals↗
PubMed2004

Evaluation of cartilage repair tissue after biomaterial implantation in rat patella by using T2 mapping.

To evaluate the ability of MR T2 mapping (8.5 T) to characterize ex vivo longitudinally, morphologically and quantitatively, alginate-based tissue engineering in a rat model of patellar cartilage chondral focal defect. Calibrated rat patellar cartilage defects (1.3 mm) were created at day 0 (D0) and alginate sponge with (Sp/C+) or without (Sp/C-) autologous chondrocytes were implanted. Animals were sacrificed sequentially at D20, D40 and D60 after surgery and dissected patellae underwent MRI exploration (8.5 T). T2 values were calculated from eight SE images by using nonlinear least-squares curve fitting on a pixel-by-pixel basis (constant repetition time of 1.5 s, eight different echo times: 5.5, 7.5, 10.5, 12.5, 15.0, 20.0, 25.0 and 30.0 ms). On the T2 map, acquired in a transversal plane through the repair zone, global T2 values and zonal variation of T2 values of repair tissue were evaluated versus control group and compared with macroscopic score and histological studies (toluidine blue, sirius red and hematoxylin-eosin). "Partial", "total" and "hypertrophic" repair patterns were identified. At D40 and D60, Sp/C+ group was characterized by a higher proportion of "total" repair in comparison to Sp/C- group. At D60, the proportion of "hypertrophic" repair was two fold in Sp/C- group versus Sp/C+ group. As confirmed morphologically and histologically, the T2 map also permitted the distinction of three types of repair tissue: "total", "partial" and "hypertrophic". "Total" repair tissue was characterized by high T2 values versus normal cartilage (p<0.05). Zonal variation, reflecting the collagen network organization, appeared only at D60 for Sp/C+ group (p<0.05). "Hypertrophic" tissue, mainly observed at D60, presented high T2 global values without zonal variation with cartilage depth. These results confirm the potency of the MR T2 map (8.5 T) to characterize macroscopically and microscopically the patterns of the scaffold guided-tissue repair of a focal chondral lesion in the rat patella ("total", "partial" and "hypertrophic"). On T2 map, three parameters (i.e. MRI macroscopic pattern, T2 global values and zonal variation of T2 values) permit to characterize chondral repair tissue, as a virtual biopsy.

Animals↗
PubMed2004

Activation of peroxisome proliferator-activated receptor alpha in rat spinal cord after peripheral noxious stimulation.

Following recurrent noxious stimulation, both functional modification and structural reorganization such as activation of the arachidonate cascade or axon sprouting occur in the central nervous system (CNS). It has been recently proposed that these alterations observed during chronic pain state were supported by an intensification of the lipid metabolism. In this regard, it has been shown that mRNA coding for several fatty acid metabolizing enzymes are up-regulated in the rat lumbar spinal cord in response to persistent nociception induced by a peripheral inflammation. As peroxisome proliferators-activated receptor (PPAR) could mediate such effects, we therefore investigated the activation of this transcription factor in the rat spinal cord following subcutaneous injection of complete Freund's adjuvant (CFA) into a hind paw. In this study, we compared the DNA-binding activity of nuclear proteins extracted from healthy and inflamed rats toward a PPAR response element. Using electrophoretic mobility-shift assay (EMSA), we found that only the PPARalpha isoform was activated in the rat spinal cord after CFA injection. This activation occurred rapidly, as early as 30 min post-CFA injection, and was persistent up to 10 h, reaching a maximum at 6h after CFA injection. In view of the consequences of PPARalpha activation in other tissues, these results suggest that fatty acid utilization is enhanced in the CNS during chronic pain state. Although the physiopathological relevance of PPARalpha activation during hyperalgesia needs further investigation, we provided here a new player in the molecular modeling of pain pathways.

Acyl-CoA Oxidase↗
PubMed2004

Redox state alteration modulates astrocyte glucuronidation.

We have investigated the effects of mild oxidative conditions on drug-metabolizing enzyme activity in rat cultured astrocytes. These experimental conditions promoting an oxidative environment were obtained by short exposure to a low concentration of menadione (5 microM) for a short duration (15 min). This resulted in the rapid and transient production of reactive oxygen species (+130%), associated with a decrease in GSH cellular content (-24%), and an increase in total protein oxidation (+26%), but promoted neither PGE(2) nor NO production. This treatment induced a rapid and persistent decrease in astrocyte glucuronidation activities, which was totally prevented by N-acetyl-l-cysteine. These oxidative conditions also affected the specific UGT1A6 activity measured in transfected V79-1A6 cells. Finally, the subsequent recovery of astrocyte glucuronidation activity may result from upregulation of UGT1A6 expression (+62%) as shown by RT-PCR and gene reporter assay. These results show that the catalytic properties and expression of cerebral UGT1A6 are highly sensitive to the redox environment. The protective effect of N-acetyl-l-cysteine suggests both a direct action of reactive oxygen species on the protein and a more delayed action on the transcriptional regulation of UGT1A6. These results suggest that cerebral metabolism can be altered by physiological or pathological redox modifications.

Animals↗