61 research outputs found

    The boron-oxygen core of borinate esters is responsible for the store-operated calcium entry potentiation ability

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    International audienceBACKGROUND: Store-Operated Calcium Entry (SOCE) is the major Ca2+ ion entry pathway in lymphocytes and is responsible of a severe combined immunodeficiency (SCID) when deficient. It has recently been observed or highlighted in other cell types such as myoblasts and neurons, suggesting a wider physiological role of this pathway. Whereas Orai1 protein is considered to be the channel allowing the SOCE in T cells, it is hypothesized that other proteins like TRPC could associate with Orai1 to form SOCE with different pharmacology and kinetics in other cell types. Unraveling SOCE cell functions requires specific effectors to be identified, just as dihydropyridines were crucial for the study of Ca2+ voltage-gated channels, or spider/snake toxins for other ion channel classes. To identify novel SOCE effectors, we analyzed the effects of 2-aminoethyl diphenylborinate (2-APB) and its analogues. 2-APB is a molecule known to both potentiate and inhibit T cell SOCE, but it is also an effector of TRP channels and endoplasmic reticulum Ca2+-ATPase. RESULTS: A structure-function analysis allowed to discover that the boron-oxygen core present in 2-APB and in the borinate ester analogues is absolutely required for the dual effects on SOCE. Indeed, a 2-APB analogue where the boron-oxygen core is replaced by a carbon-phosphorus core is devoid of potentiating capacity (while retaining inhibition capacity), highlighting the key role of the boron-oxygen core present in borinate esters for the potentiation function. However, dimesityl borinate ester, a 2-APB analogue with a terminal B-OH group showed an efficient inhibitory ability, without any potentiating capacity. The removal or addition of phenyl groups respectively decrease or increase the efficiency of the borinate esters to potentiate and inhibit the SOCE. mRNA expression revealed that Jurkat T cells mainly expressed Orai1, and were the more sensitive to 2-APB modulation of SOCE. CONCLUSIONS: This study allows the discovery of new boron-oxygen core containing compounds with the same ability as 2-APB to both potentiate and inhibit the SOCE of different leukocyte cell lines. These compounds could represent new tools to characterize the different types of SOCE and the first step in the development of new immunomodulators

    Permeation, regulation and control of expression of TRP channels by trace metal ions

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    Moraxella lacunata: a rare cause of infective endocarditis

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    We describe the first case of Moraxella lacunata definite native valve endocarditis in a patient with previously normal mitral valves. The disease was complicated with embolizations of the brain and spleen. After 6 weeks of antimicrobial treatment, valvular replacement was performed. The clinical course and diagnostic findings suggest that Moraxella lacunata possesses high aggressiveness leading to progressive valvular destruction and embolizations

    Low and intermediate level image processing on SYMPATIX, a SIMD parallel computer

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    SIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : RM 1141 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc
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