Institution
French Institute of Health and Medical Research
Government•Paris, France•
About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.
Topics: Population, Receptor, Gene, Immune system, Antigen
Papers published on a yearly basis
Papers
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TL;DR: In this paper, four ligands from Mycobacterium tuberculosis strain H37Rv that stimulated proliferation of a major human gamma delta T cell subset were isolated and partially characterized.
Abstract: Most human peripheral blood gamma delta T lymphocytes respond to hitherto unidentified mycobacterial antigens. Four ligands from Mycobacterium tuberculosis strain H37Rv that stimulated proliferation of a major human gamma delta T cell subset were isolated and partially characterized. One of these ligands, TUBag4, is a 5' triphosphorylated thymidine-containing compound, to which the three other stimulatory molecules are structurally related. These findings support the hypothesis that some gamma delta T cells recognize nonpeptidic ligands.
693 citations
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TL;DR: The data provide evidence that HDAC‐6 might act as a dual deacetylase for tubulin and histones, and suggest the possibility that acetylated non‐histone proteins might represent novel targets for pharmacological therapy by HDAC inhibitors.
Abstract: Microtubules are cylindrical cytoskeletal structures found in almost all eukaryotic cell types which are involved in a great variety of cellular processes. Reversible acetylation on the ϵ‐amino group of α‐tubulin Lys40 marks stabilized microtubule structures and may contribute to regulating microtubule dynamics. Yet, the enzymes catalysing this acetylation/deacetylation have remained unidentified until recently. Here we report that β‐tubulin interacts with histone deacetylase‐6 (HDAC‐6) in a yeast two‐hybrid assay and in vitro . We find that HDAC‐6 is a micro tubule‐associated protein capable of deacetylating α‐tubulin in vivo and in vitro . HDAC‐69s microtubule binding and deacetylation functions both depend on the hdac domains. Overexpression of HDAC‐6 in mammalian cells leads to tubulin hypoacetylation. In contrast, inhibition of HDAC‐6 function by two independent mechanisms—pharmacological (HDAC inhibitors) or genetic (targeted inactivation of HDAC‐6 in embryonic stem cells)—leads to hyperacetylation of tubulin and microtubules. Taken together, our data provide evidence that HDAC‐6 might act as a dual deacetylase for tubulin and histones, and suggest the possibility that acetylated non‐histone proteins might represent novel targets for pharmacological therapy by HDAC inhibitors.
693 citations
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TL;DR: It is demonstrated that ROS are second messengers involved in leptin‐induced signaling in endothelial cells, which may activate atherogenic processes and contribute to the development of vascular pathology.
Abstract: Human umbilical vein endothelial cells (HUVEC) express functional receptors to leptin, the product of the ob gene. As human obesity is associated with atherosclerosis and hyperleptinemia, we investigated whether leptin, in addition to its angiogenic properties, exerts atherogenic effects through the generation of oxidative stress in endothelial cells. In HUVEC leptin increased the accumulation of reactive oxygen species (ROS), as assessed by the oxidation of 2', 7'- dichlorodihydrofluorescein, in a time- and concentration-dependent manner. In addition, leptin activated the NH2-terminal c-Jun kinase/stress-activated protein kinase pathway as demonstrated by enhanced JNK activity and AP-1 DNA binding. Both effects were sensitive to antioxidant treatment with N-acetylcysteine. NF-kappaB, another redox-sensitive transcription factor, was also activated by leptin stimulation in an oxidant-dependent manner. Finally, activation of both AP-1 and NF-kappaB was associated with an enhanced expression of the monocyte chemoattractant protein-1 in HUVEC. These findings demonstrate that ROS are second messengers involved in leptin-induced signaling in endothelial cells. Thus, chronic oxidative stress in endothelial cells under hyperleptinemia may activate atherogenic processes and contribute to the development of vascular pathology.
693 citations
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TL;DR: It is suggested that autoimmune disease, even one that is organ specific, can occur when mobilization of an adaptive immune response results in runaway activation of the innate response.
693 citations
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TL;DR: The data suggest that a reduction in frataxin results in oxidative damage, given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies.
Abstract: Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel frataxin function we developed monoclonal antibodies raised against different regions of the protein. These antibodies detect a processed 18 kDa protein in various human and mouse tissues and cell lines that is severely reduced in Friedreich ataxia patients. By immunocytofluorescence and immunocytoelectron microscopy we show that frataxin is located in mitochondria, associated with the mitochondrial membranes and crests. Analysis of cellular localization of various truncated forms of frataxin expressed in cultured cells and evidence of removal of an N-terminal epitope during protein maturation demonstrated that the mitochondrial targetting sequence is encoded by the first 20 amino acids. Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage.
693 citations
Authors
Showing all 109539 results
Name | H-index | Papers | Citations |
---|---|---|---|
Guido Kroemer | 236 | 1404 | 246571 |
Pierre Chambon | 211 | 884 | 161565 |
Peer Bork | 206 | 697 | 245427 |
Ronald M. Evans | 199 | 708 | 166722 |
Raymond J. Dolan | 196 | 919 | 138540 |
Matthew Meyerson | 194 | 553 | 243726 |
Charles A. Dinarello | 190 | 1058 | 139668 |
Julie E. Buring | 186 | 950 | 132967 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Didier Raoult | 173 | 3267 | 153016 |
Giuseppe Remuzzi | 172 | 1226 | 160440 |
Zena Werb | 168 | 473 | 122629 |
Nahum Sonenberg | 167 | 647 | 104053 |
Philippe Froguel | 166 | 820 | 118816 |
Gordon J. Freeman | 164 | 579 | 105193 |