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Theresa Riebeling Kunzah Jamal Rebecca Wilson Benedikt Kolbrink Friedrich Alexander von Samson-Himmelstjerna Caroline Moerke Laura Ramos Garcia Eileen Dahlke Friederike Michels Fred Lühder Domagoj Schunk Philipp Doldi Bartosz Tyczynski Andreas Kribben Charlotte Flüh Franziska Theilig Ulrich Kunzendorf Pascal Meier Stefan Krautwald 《Cell death and differentiation》2021,28(5):1610
The receptor-interacting serine/threonine protein kinase 1 (RIPK1) is a key mediator of regulated cell death and inflammation. Recent studies suggest that RIPK1 inhibition would fundamentally improve the therapy of RIPK1-dependent organ damage in stroke, myocardial infarction, kidney failure, and systemic inflammatory response syndrome. Additionally, it could ameliorate or prevent multi-organ failure induced by cytokine release in the context of hyperinflammation, as seen in COVID-19 patients. Therefore, we searched for a RIPK1 inhibitor and present the aromatic antiepileptic and FDA-approved drug primidone (Liskantin®) as a potent inhibitor of RIPK1 activation in vitro and in a murine model of TNFα-induced shock, which mimics the hyperinflammatory state of cytokine release syndrome. Furthermore, we detected for the first time RIPK1 activation in the respiratory tract epithelium of hospitalized patients who tested positive for SARS-CoV-2 infection. Our data provide a strong rationale for evaluating the drug primidone in conditions of hyperinflammation in humans.Subject terms: Cell death and immune response, Translational research 相似文献
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Friederike Koenig 《Photosynthesis research》1990,26(1):29-37
Growth of Anacystis in high light in the presence of sublethal concentrations of DCMU-type inhibitors leads to an increased synthesis of phycocyanin paralleled by a reduced rate of 35S methionine incorporation into the D1 protein compared to the high light controls, as is characteristic for naturally-induced shade phenotype. On the contrary, sun phenotype is characterized by a low rate of antenna synthesis, but a high rate of 35S methionine incorporation into the D1 protein.Room temperature excitation spectra of 684 nm fluorescence emission clearly demonstrate the participation of the extraordinarily high concentration of phycocyanin in artificially shade-adapted cells in excitation energy transfer to chlorophyll.It could be shown that the development of shade-type appearance is not simply the consequence of an imbalance in electron transport, since an addition of thiosulphate to cultures growing in high light in the presence of DCMU-type inhibitors can only partially prevent or revert the change from sun to artificial-herbicide-induced-shade phenotype. This is regarded as evidence that the dynamic herbicide-binding D1 protein itself may play a role as a light meter in the process of natural shade adaptation, the rate of its degradation and resynthesis possibly giving the signal for the adaptive reorganization of the photosynthetic apparatus. The chain of signal transduction remains to be established.Abbreviations atrazine
2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine
- chl
chlorophyll
- D1
reaction center polypeptide carrying the secondary plastoquinone electron acceptor of PS II
- DCMU
3-(3,4-dichlorophenyl)-1,1-dimethylurea
- PAGE
polyacrylamide gel electrophoresis
- PAR
photosynthetically active radiation
- PC
phycocyanin
- PCC
Pasteur Culture Collection
- PS
photosystem
- QB
secondary plastoquinone electron acceptor of PS II
- SAUG
Sammlung von Algenkulturen am Pflanzenphysiologischen Institut der Universtität Göttingen
- SDS
sodium dodecyl sulphate
Dedicated to Professor Wilhelm Menke on the occasion of his 80th birthday. 相似文献
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