RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/33971320http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33971320http://www.w3.org/2000/01/rdf-schema#comment"

Background

CD137 signaling is an essential factor in cell fate and atherosclerosis. An increase in the number of apoptotic macrophages accelerates atherosclerotic development involving mitochondrial dynamics.However, the role of CD137 signaling in macrophage apoptosis and changes in mitochondria has not been demonstrated clearly.

Methods and results

Here, we used ApoE-/- mice as a model of atherosclerotic plaques. Mouse agonist anti-CD137 L and inhibitory anti-CD137 antibody were used to activate or block the CD137 signaling, respectively. Treatment of ApoE-/- mice with agonist anti-CD137 L promoted the formation of necrotic cores and macrophage apoptosis in plaques. Further, activation of CD137 signaling caused macrophage apoptosis in vitro, with upregulation of caspase-9 and caspase-3 expression and an increase in the Bax/Bcl-2 ratio. Meanwhile, CD137 signaling promoted mitochondrial fission observed by mitochondrial fragmentation. Interestingly, inhibition of mitochondrial dynamin-related protein 1 (Drp1) using Mdivi-1 reduced the expression of pro-apoptotic proteins and the amounts of apoptotic macrophages induced by CD137 signaling. Finally, we also found that the p38 MAPK pathway activated by CD137 signaling increased the expression of Drp1 expression and number of mitochondrial fragmented structures. Inhibition of the p38 MAPK pathway by SB203580 attenuated mitochondrial dysfunction through reducing mitochondrial membrane potential loss, cytochrome c release, and mitochondrial reactive oxygen species (ROS) generation.

Conclusions

Overall, we identify a novel mechanism whereby CD137 signaling induces macrophage apoptosis through promoting mitochondrial fission dependent on the p38 MAPK pathway."xsd:string
http://purl.uniprot.org/citations/33971320http://purl.org/dc/terms/identifier"doi:10.1016/j.biocel.2021.106003"xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/author"Li B."xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/author"Zhang Y."xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/author"Xu Y."xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/author"Yuan W."xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/author"Xia H."xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/author"Xu Y.'"xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/author"Zang G."xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/name"Int J Biochem Cell Biol"xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/pages"106003"xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/title"Activation of CD137 signaling promotes macrophage apoptosis dependent on p38 MAPK pathway-mediated mitochondrial fission."xsd:string
http://purl.uniprot.org/citations/33971320http://purl.uniprot.org/core/volume"136"xsd:string
http://purl.uniprot.org/citations/33971320http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33971320
http://purl.uniprot.org/citations/33971320http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33971320
http://purl.uniprot.org/uniprot/#_P20334-mappedCitation-33971320http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33971320
http://purl.uniprot.org/uniprot/#_Q3U3R1-mappedCitation-33971320http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33971320
http://purl.uniprot.org/uniprot/#_Q8R037-mappedCitation-33971320http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33971320
http://purl.uniprot.org/uniprot/Q8R037http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33971320
http://purl.uniprot.org/uniprot/P20334http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33971320
http://purl.uniprot.org/uniprot/Q3U3R1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33971320