Interleukin 6 Knockout Inhibits Aging-Related Accumulation of p53 in the Mouse Myocardium

Abstract Interleukin 6 (IL6) and p53 are linked by mutual regulatory mechanisms and are both upregulated in aging. The aim of this study was to evaluate the effects of aging and IL6 on expression of p53 in the mouse heart. Male C57BL6/J wild-type and IL6 knockout mice at the age of 4–5 months (young...

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Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2019-01, Vol.74 (2), p.176-182
Main Authors: Bonda, Tomasz A, Dziemidowicz, Magdalena, Cieślińska, Magdalena, Tarasiuk, Ewa, Wawrusiewicz-Kurylonek, Natalia, Bialuk, Izabela, Winnicka, Maria M, Kamiński, Karol A
Format: Article
Language:English
Subjects:
Aging
Aging - genetics
Aging - metabolism
AKT protein
Animals
Blotting, Western
Cyclin-dependent kinase inhibitor p21
Echocardiography
Enzyme-Linked Immunosorbent Assay
Gene expression
Gene Expression Regulation
Genotype & phenotype
GTP-binding protein
Heart
Heart Ventricles - diagnostic imaging
Heart Ventricles - metabolism
Heart Ventricles - physiopathology
Interleukin 6
Interleukin-6 - blood
Localization
Male
MDM2 protein
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Fluorescence
Myocardium
Myocardium - metabolism
Myocardium - pathology
p53 Protein
Phenotypes
Polymerase chain reaction
Post-transcription
Proteasomes
Protein expression
Random Allocation
Real-Time Polymerase Chain Reaction
RNA, Messenger - genetics
Tumor Suppressor Protein p53 - biosynthesis
Tumor Suppressor Protein p53 - genetics
Ventricular Function, Left
Western blotting
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Summary:Abstract Interleukin 6 (IL6) and p53 are linked by mutual regulatory mechanisms and are both upregulated in aging. The aim of this study was to evaluate the effects of aging and IL6 on expression of p53 in the mouse heart. Male C57BL6/J wild-type and IL6 knockout mice at the age of 4–5 months (young adult) and 24–30 months (old) were used. Myocardial expression of proteins such as p53, p21, Mdm2, and phospho-Akt/Akt was estimated using Western blotting and expression of p53 and p21 mRNA using real-time polymerase chain reaction. Expression of p53 protein was lower in IL6 knockout hearts than in wild-type hearts. Aging caused significant upregulation of p53 protein level; however, it was significantly higher in old wild-type hearts than in old IL6 knockout hearts (p < .05). Similar p53 mRNA levels in all groups implied IL6 influence on age-related proteasomal degradation of p53. Localization of p53 mainly in the extranuclear compartment and lack of p21 upregulation in aged hearts may suggest quenched transcriptional activity of p53 despite increased abundance of p53. We conclude that lack of IL6 attenuates expression of p53 protein in the hearts of young mice and diminishes its accumulation with aging by post-transcriptional mechanisms; however, this is not related to altered phenotype of aging heart.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/gly105