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AuthorGompf, Annedc.contributor.author
Date of accession2016-03-15T06:23:54Zdc.date.accessioned
Available in OPARU since2016-03-15T06:23:54Zdc.date.available
Year of creation2011dc.date.created
AbstractWith successive telomere shortening late generation Telomerase knockout mice prematurely develop aging symptoms like a senescence-associated secretory phenotype, myeloproliferation, reduced body weight, crypt atrophy in the intestine and have a shortened life expectancy. A candidate molecule for mediating these aging symptoms is MK2, a direct target of the MAP kinase p alpha/ß. Besides regulating several cytokines and other mediators, its participation in hematopoiesis and inflammatory diseases, as wells as its contribution to DNA damage signaling and cell cycle arrest, MK2 could also be involved in metabolism. To this end the influence of MK2 on accelerated aging due to telomere shorting has been analyzed in the mouse model of telomerase and MK2 double knockout. We hypothesized that elimination of MK2 could prevent activation of p53/p21 after telomere-shorting induced DNA damage leading to senescence and apoptosis and thereby prevent tissue damage, but could not confirm this hypothesis. Despite reduced activation of p53/p21 in the intestinal epithelium of double knockout mice the intestine was structurally damaged. The nutrient deficiency of Telomerase knockout mice, of which signs are increased growth hormone secretion and simultaneous growth hormone resistance, was exacerbated by loss of MK2 presumably as an effect of disturbed gluconeogenesis. Nevertheless, survival of Telomerase knockout mice was not altered by the absence of MK2. Nor could the systemic inflammation be improved by disruption of p38/MK2 signaling in Telomerase deficient mice, recognizable in the persisting biased cytokine environment and the prevalence of innate immune system cells. The reduction of inflammation factors in the blood plasma paralleled by an increase in growth hormone secretion by MK2 deficiency did not prevent the development of granulocytosis seen in the Telomere dysfunctional background, although splenomegaly could be prevented by reduction of hematopoietic cell proliferation.dc.description.abstract
Languagededc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 01.10.2008)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v2dc.rights.uri
KeywordMK2dc.subject
KeywordMyeloproliferationdc.subject
KeywordSASPdc.subject
KeywordTelomerdysfunktiondc.subject
Dewey Decimal GroupDDC 570 / Life sciencesdc.subject.ddc
LCSHMicedc.subject.lcsh
MeSHAspartic acid endopeptidasesdc.subject.mesh
MeSHMK2 protein, humandc.subject.mesh
TitleMAPKAPK2-Deletion führt zur partiellen Normalisierung des sekretorischen Phänotypen in Telomer-dysfunktionellen Mäusen ohne Auswirkung auf Organerhalt und Überlebendc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-1920dc.identifier.doi
PPN666464804dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-77133dc.identifier.urn
GNDTelomerasedc.subject.gnd
FacultyFakultät für Naturwissenschaftenuulm.affiliationGeneral
Date of activation2011-07-26T08:27:43Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 14.135; W: W-H 12.598uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS ID7713uulm.vtsID
CategoryPublikationenuulm.category
Bibliographyuulmuulm.bibliographie


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