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- Ammoun, Sylwia, et al.
(author)
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OX1 orexin receptors activate extracellular signal-regulated kinase in Chinese hamster ovary cells via multiple mechanisms : the role of Ca2+ influx in OX1 receptor signaling
- 2006
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In: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 20:1, s. 80-99
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Journal article (peer-reviewed)abstract
- Activation of OX1 orexin receptors heterologously expressedin Chinese hamster ovary (CHO) cells led to a rapid, strong,and long-lasting increase in ERK phosphorylation (activation).Dissection of the signal pathways to ERK using multiple inhibitorsand dominant-negative constructs indicated involvement of Ras,protein kinase C, phosphoinositide-3-kinase, and Src. Most interestingly,Ca2+ influx appeared central for the ERK response in CHO cells,and the same was indicated in recombinant neuro-2a cells andcultured rat striatal neurons. Detailed investigations in CHOcells showed that inhibition of the receptor- and store-operatedCa2+ influx pathways could fully attenuate the response, whereasinhibition of the store-operated Ca2+ influx pathway alone orthe Ca2+ release was ineffective. If the receptor-operated pathwaywas blocked, an exogenously activated store-operated pathwaycould take its place and restore the coupling of OX1 receptorsto ERK. Further experiments suggested that Ca2+ influx, as such,may not be required for ERK phosphorylation, but that Ca2+,elevated via influx, acts as a switch enabling OX1 receptorsto couple to cascades leading to ERK phosphorylation, cAMP elevation,and phospholipase C activation. In conclusion, the data suggestthat the primary coupling of orexin receptors to Ca2+ influxallows them to couple to other signal pathways; in the absenceof coupling to Ca2+ influx, orexin receptors can act as signalintegrators by taking advantage of other Ca2+ influx pathways.
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- Demuth, Andreas, et al.
(author)
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Pathogenomics: An updated European Research Agenda
- 2008
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In: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-7257 .- 1567-1348. ; 8:3, s. 386-393
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Journal article (peer-reviewed)abstract
- The emerging genomic technologies and bioinformatics provide novel opportunities for studying life-threatening human pathogens and to develop new applications for the improvement of human and animal health and the prevention, treatment, and diagnosis of infections. Based on the ecology and population biology of pathogens and related organisms and their connection to epidemiology, more accurate typing technologies and approaches will lead to better means of disease control. The analysis of the genome plasticity and gene pools of pathogenic bacteria including antigenic diversity and antigenic variation results in more effective vaccines and vaccine implementation programs. The study of newly identified and uncultivated microorganisms enables the identification of new threats. The scrutiny of the metabolism of the pathogen in the host allows the identification of new targets for anti-infectives and therapeutic approaches. The development of modulators of host responses and mediators of host damage will be facilitated by the research on interactions of microbes and hosts, including mechanisms of host damage, acute and chronic relationships as well as commensalisms. The study of multiple pathogenic and non-pathogenic microbes interacting in the host will improve the management of multiple infections and will allow probiotic and prebiotic interventions. Needless to iterate, the application of the results of improved prevention and treatment of infections into clinical tests will have a positive impact on the management of human and animal disease. The Pathogenomics Research Agenda draws on discussions with experts of the Network of Excellence "EuroPathoGenomics" at the management board meeting of the project held during 18-21 April 2007, in the Villa Vigoni, Menaggio, Italy. Based on a proposed European Research Agenda in the field of pathogenomics by the ERA-NET PathoGenoMics the meeting's participants updated the established list of topics as the research agenda for the future.
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- Zhu, Changlian, 1964, et al.
(author)
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X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial antioxidants.
- 2007
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In: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 26:12, s. 3402-10
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Journal article (peer-reviewed)abstract
- We demonstrate that X chromosome-linked inhibitor of apoptosis protein (XIAP) counteracts oxidative stress in two essentially different disease-related models of brain injury, hypoxia-ischemia and irradiation, as judged by lower expression of nitrotyrosine (5-fold) and 4-hydroxy-2-nonenal (10-fold) in XIAP-overexpressing compared with wild-type mice. XIAP overexpression induced up-regulation of at least three antioxidants residing in mitochondria, superoxide dismutase 2, thioredoxin 2 and lysine oxoglutarate reductase. Cytochrome c release from mitochondria was reduced in XIAP-overexpressing mice. Hence, in addition to blocking caspases, XIAP can regulate reactive oxygen species in the brain, at least partly through up-regulation of mitochondrial antioxidants. XIAP-induced prevention of oxidative stress was not secondary to tissue protection because although XIAP overexpression provides tissue protection after hypoxia-ischemia, it does not prevent tissue loss after irradiation. This is a previously unknown role of XIAP and may provide the basis for development of novel protective strategies for both acute and chronic neurodegenerative diseases, where oxidative stress is an integral component of the injury mechanisms involved.
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