Interaction between the ins/IGF-1 and p38 MAPK signaling pathways in molecular compensation of sod genes and modulation related to intracellular ROS levels in C. elegans
| Autor: | Naoaki Ishii, Kayo Yasuda, Sumino Yanase |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
sod genes Mutant Biophysics Oxidative phosphorylation ins/IGF-1 signaling medicine.disease_cause Biochemistry lcsh:Biochemistry Superoxide dismutase 03 medical and health sciences 0302 clinical medicine medicine lcsh:QD415-436 lcsh:QH301-705.5 Gene Transcription factor biology Chemistry Molecular compensation Cell biology 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis biology.protein C. elegans p38 MAPK signaling Intracellular Relaxin/insulin-like family peptide receptor 2 Oxidative stress Insulin-like peptide Research Article |
| Zdroj: | Biochemistry and Biophysics Reports Biochemistry and Biophysics Reports, Vol 23, Iss, Pp 100796-(2020) |
| ISSN: | 2405-5808 |
| Popis: | Superoxide dismutases, which catalytically remove intracellular superoxide radicals by the disproportionation of molecular oxygen and hydrogen peroxide, are encoded by the sod-1 to -5 genes in the nematode C. elegans. Expression of the sod genes is mutually compensatory for the modulation of intracellular oxidative stress during aging. Interestingly, several-fold higher expression of the sod-1 to -4 was induced in a sod-5 deletion mutant, despite the low expression levels of sod-5 in wild-type animals. Consequently, this molecular compensation facilitated recovery of lifespan in the sod-5 mutant. In previous reports, two transcription factors DAF-16 and SKN-1 are associated with the compensatory expression of sod genes, which are downstream targets of the ins/IGF-1 and p38 MAPK signaling pathways activated under oxidative and heavy metal stresses, respectively. Here, we show that p38 MAPK signaling regulates induction of not only the direct expression of sod-1, -2 and -4 but also the indirect modulation of DAF-16 targets, such as sod-3 and -5 genes. Moreover, a SKN-1 target, the insulin peptide gene ins-5, partially mediates the expression of DAF-16 targets via p38 MAPK signaling. These findings suggest that the interaction of ins/IGF-1 and p38 MAPK signaling pathways plays an important role in the fine-tuning of molecular compensation among sod genes to protect against mitochondrial oxidative damage during aging. Highlights • Mitochondrial ROS is removed by SODs during aging. • Expression of sod genes in C. elegans related to lifespan maintenance. • Interaction of the ins/IGF-1 and p38 MAPK signalings regulates the fine-tuning of sod genes expression. • ins-5 of SKN-1 target encodes an agonist of ins/IGF-1 signaling. |
| Databáze: | OpenAIRE |
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