{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Panagopoulou P"],"funding":["NHLBI NIH HHS"],"pagination":["761-75"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2396798"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["181(5)"],"pubmed_abstract":["We explored the involvement of the muscle-specific intermediate filament protein desmin in the model of tumor necrosis factor alpha (TNF-alpha)-induced cardiomyopathy. We demonstrate that in mice overexpressing TNF-alpha in the heart (alpha-myosin heavy chain promoter-driven secretable TNF-alpha [MHCsTNF]), desmin is modified, loses its intercalated disk (ID) localization, and forms aggregates that colocalize with heat shock protein 25 and ubiquitin. Additionally, other ID proteins such as desmoplakin and beta-catenin show similar localization changes in a desmin-dependent fashion. To address underlying mechanisms, we examined whether desmin is a substrate for caspase-6 in vivo as well as the implications of desmin cleavage in MHCsTNF mice. We generated transgenic mice with cardiac-restricted expression of a desmin mutant (D263E) and proved that it is resistant to caspase cleavage in the MHCsTNF myocardium. The aggregates are diminished in these mice, and D263E desmin, desmoplakin, and beta-catenin largely retain their proper ID localization. Importantly, D263E desmin expression attenuated cardiomyocyte apoptosis, prevented left ventricular wall thinning, and improved the function of MHCsTNF hearts."],"journal":["The Journal of cell biology"],"pubmed_title":["Desmin mediates TNF-alpha-induced aggregate formation and intercalated disk reorganization in heart failure."],"pmcid":["PMC2396798"],"funding_grant_id":["R01 HL073017","P50 HL-O6H","R01 HL058081","R01 HL73017","R01 HL58081"],"pubmed_authors":["Capetanaki Y","Davos CH","Milner DJ","Mann DL","Varela E","Cameron J","Panagopoulou P"],"additional_accession":[]},"is_claimable":false,"name":"Desmin mediates TNF-alpha-induced aggregate formation and intercalated disk reorganization in heart failure.","description":"We explored the involvement of the muscle-specific intermediate filament protein desmin in the model of tumor necrosis factor alpha (TNF-alpha)-induced cardiomyopathy. We demonstrate that in mice overexpressing TNF-alpha in the heart (alpha-myosin heavy chain promoter-driven secretable TNF-alpha [MHCsTNF]), desmin is modified, loses its intercalated disk (ID) localization, and forms aggregates that colocalize with heat shock protein 25 and ubiquitin. Additionally, other ID proteins such as desmoplakin and beta-catenin show similar localization changes in a desmin-dependent fashion. To address underlying mechanisms, we examined whether desmin is a substrate for caspase-6 in vivo as well as the implications of desmin cleavage in MHCsTNF mice. We generated transgenic mice with cardiac-restricted expression of a desmin mutant (D263E) and proved that it is resistant to caspase cleavage in the MHCsTNF myocardium. The aggregates are diminished in these mice, and D263E desmin, desmoplakin, and beta-catenin largely retain their proper ID localization. Importantly, D263E desmin expression attenuated cardiomyocyte apoptosis, prevented left ventricular wall thinning, and improved the function of MHCsTNF hearts.","dates":{"release":"2008-01-01T00:00:00Z","publication":"2008 Jun","modification":"2025-04-18T14:19:10.587Z","creation":"2019-03-27T00:15:17Z"},"accession":"S-EPMC2396798","cross_references":{"pubmed":["18519735"],"doi":["10.1083/jcb.200710049"]}}