2 research outputs found
Transport dâiode par le transporteur de sodium/acide monocarboxylique SMCT1
Le transporteur de Na+/ acide monocarboxylique sensible Ă lâibuprofĂšne (SMCT1) est exprimĂ© dans la membrane apicale de plusieurs Ă©pithĂ©lia. Son rĂŽle physiologique dans la glande thyroĂŻde reste cependant obscur mais on prĂ©sume quâil pourrait agir comme un transporteur apical dâiode nĂ©cessaire pour la synthĂšse des hormones thyroĂŻdiennes. RĂ©cemment, on a montrĂ© que SMCT1 possĂšde un courant de fuite anionique sensible Ă [Na+]e qui permettrait de transporter lâiode de façon Ă©lectrogĂ©nique. Cependant, un efflux dâiode sensible Ă lâibuprofĂšne, mais indĂ©pendant de la [Na+]e a Ă©tĂ© aussi observĂ© sur des cultures primaires des thyrocytes porcins, suggĂ©rant un autre mĂ©canisme de transport dâiode par SMCT1. Ce travail vise Ă comprendre les caractĂ©ristiques de ce genre de transport en utilisant comme modĂšle dâexpression les ovocytes de Xenopus laevis. Les rĂ©sultats obtenus des essais de captation dâiode radioactif montrent que SMCT1 prĂ©sente un transport dâiode sensible Ă lâibuprofĂšne de lâordre de 30nmol/ovocyte/h. Si ce transport est non saturable en iode (0-100 mM), il nĂ©cessite du Na+ dans la solution externe. En effet, le remplacement du Na+ extracellulaire par le NMDG inhibe complĂštement le transport. En outre, on sâest intĂ©ressĂ© Ă exclure la possibilitĂ© de diffĂ©rents artefacts. En ayant trouvĂ© que la grande majoritĂ© de lâiode radioactif se trouve dans la partie soluble de lâovocyte, on exclut une liaison non spĂ©cifique de lâiode Ă la membrane cellulaire. Cependant, une bonne proportion de lâiode transportĂ© pourrait ĂȘtre liĂ©e Ă des protĂ©ines Ă lâintĂ©rieur de l`ovocyte. En effet, on observe une rĂ©duction du transport dâiode dans les ovocytes exprimant SMCT1 de 81,6 ± 2 % en prĂ©sence de 2 % BSA dans la solution extracellulaire. Ăgalement, on Ă©carte la possibilitĂ© que le transport dâiode soit le rĂ©sultat de la surexpression de protĂ©ines de transport endogĂšnes dont les canaux chlore. Le transport dâiode semble spĂ©cifique Ă lâexpression de SMCT1 et de maniĂšre intĂ©ressante Ă lâexpression dâun autre transporteur de monocarboxylates, MCT1. Lâanalyse de lâensemble des essais, y compris le fait que lâamplitude du transport observĂ© est 20 fois plus grande que celle du courant de fuite nous mĂšne Ă proposer que SMCT1 puisse transporter lâiode de façon Ă©lectroneutre. Cependant, le mĂ©canisme par lequel ceci est accompli nâest pas Ă©vident Ă identifier. Lâutilisation dâun autre modĂšle cellulaire serait surement utile pour rĂ©pondre Ă cette question.Ibuprofen sensitive, Sodium Monocarboxylate Transporter (SMCT1) is expressed in the apical membrane of diverse epithelia. Its physiological role in the thyroid remains however unknown, but it has been proposed that SMCT1 could act as an apical iodide transporter required for the main function of the gland: the thyroid hormone synthesis.
We previously reported that SMCT1 exhibit a [Na+]e sensible anionic leak current that could account for the electrogenic transport of iodide. However, an iodine efflux sensitive to ibuprofen but independent of [Na+]e, was also observed in primary cultures of porcine thyrocytes, suggesting another mechanism of iodine transport mediated by SMCT1. This work aims to understand the characteristics of this type of transport using Xenopus laevis oocytes as an SMCT1 expression system. By realising 125I uptakes, we found that SMCT1 transports iodide in an ibuprofen sensitive manner (30nmol/oocyte/h). While nonsaturable uptake iodide kinetics were observed, SMCT1 iodide transport was Na+ dependent as shown by the transport reduction when the [Na+]e is replaced by NMDG. The possibility of artifacts, such as non specific binding and the overexpression of endogenous proteins, was analysed. By observing that the vast majority of the radioactive iodide is found in the soluble portion of the oocyte, we excluded non-specific binding of iodide to the cell membrane. However, it is believed that most of the iodide entering the cell is not free and must be bound to some intracellular proteins. Indeed, there is a significant reduction of SMCT1-mediated iodide transport when 2% BSA is present at the extracellular solution. Furthermore, the lack of iodide transport when overexpressing other proteins than SMCT1, precludes the possibility of an overexpression of endogenous transport proteins like chloride channels for example. In fact, the transport of iodide appears to be specific to the expression of SMCT1 and interestingly of another monocarboxylate transporter MCT1. The analysis of all trials, including the fact that the amplitude of the observed transport is 20 times larger than the leak current lead us to propose that SMCT1 can carry iodide in an electroneutral manner. However, the mechanism by which this is accomplished is not easy to identify and future experiments will be necessary to determine whether this transport is observed in other SMCT1 expression systems
How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort
CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women