Novel Role of Mammalian Cell Senescence-Sustenance of Muscle Larvae of Trichinella spp

Author:

Dabrowska Magdalena1ORCID,Kępczyńska Agnieszka2,Goździk Katarzyna3,Całka-Kresa Małgorzata4,Skoneczny Marek5,Zieliński Zbigniew6,Doligalska Maria3,Sikora Ewa1

Affiliation:

1. Laboratory of Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa 02-093, Poland

2. Laboratory of Electron Microscopy, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa 02-093, Poland

3. Department of Parasitology, Institute of Functional Biology and Ecology, Faculty of Biology, University of Warsaw, Warszawa 02-089, Poland

4. Laboratory of Imaging Tissue Structure and Function, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa 02-093, Poland

5. Laboratory of Yeast Genetics and Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa 02-106, Poland

6. Laboratory of Molecular Bases of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa 02-093, Poland

Abstract

Muscle larva of the parasitic nematode Trichinella spp. lives in a portion of muscle fibre transformed to a nurse cell (NC). Based on our previous transcriptomic studies, NC growth arrest was inferred to be accompanied by cellular senescence. In the current study, NC was proven to display the following markers of senescence: high senescence-associated β-galactosidase activity, lipid deposition, DNA damage, and cell cycle inhibition. Moreover, the nuclear localization of Activator Protein 1 (c-Fos, c-Jun, and FosB), as well as the upregulation of numerous AP-1 target genes in the NC, remained in accord with AP-1 recently identified as a master transcription factor in senescence. An increase in reactive oxygen species generation and the upregulation of antioxidant defence enzymes, including glutathione peroxidases 1 and 3, catalase, superoxide dismutases 1 and 3, and heme oxygenase 1, indicated an ongoing oxidative stress to proceed in the NC. Interestingly, antioxidant defence enzymes localized not only to the NC but also to the larva. These results allowed us to hypothesize that oxidative stress accompanying muscle regeneration and larval antigenic properties lead to the transformation of a regenerating myofibre into a senescent cell. Cellular senescence apparently represents a state of metabolism that sustains the long-term existence of muscle larva and ultimately provides it with the antioxidant capacity needed during the next host colonization. Senotherapy, a therapeutic approach aimed at selective elimination of senescent cells, can thus be viewed as potentially effective in the treatment of trichinosis.

Funder

Nencki Institute of Experimental Biology

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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