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Changes in autophagy, proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells.
Oncotarget 2015; 6(37):39457-68O

Abstract

A sharp definition of what a senescent cell is still lacking since we do not have in depth understanding of mechanisms that induce cellular senescence. In addition, senescent cells are heterogeneous, in that not all of them express the same genes and present the same phenotype. To further clarify the classification of senescent cells, hints may be derived by the study of cellular metabolism, autophagy and proteasome activity. In this scenario, we decided to study these biological features in senescence of Mesenchymal Stromal Cells (MSC). These cells contain a subpopulation of stem cells that are able to differentiate in mesodermal derivatives (adipocytes, chondrocytes, osteocytes). In addition, they can also contribute to the homeostatic maintenance of many organs, hence, their senescence could be very deleterious for human body functions. We induced MSC senescence by oxidative stress, doxorubicin treatment, X-ray irradiation and replicative exhaustion. The first three are considered inducers of acute senescence while extensive proliferation triggers replicative senescence also named as chronic senescence. In all conditions, but replicative and high IR dose senescence, we detected a reduction of the autophagic flux, while proteasome activity was impaired in peroxide-treated and irradiated cells. Differences were observed also in metabolic status. In general, all senescent cells evidenced metabolic inflexibility and prefer to use glucose as energy fuel. Irradiated cells with low dose of X-ray and replicative senescent cells show a residual capacity to use fatty acids and glutamine as alternative fuels, respectively. Our study may be useful to discriminate among different senescent phenotypes.

Authors+Show Affiliations

Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.Institute of Bioscience and Bioresources, CNR, Naples, Italy. Department of Clinical and Experimental Medicine and Surgery, Division of Neurology, Second University of Naples, Naples, Italy.Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.Institute of Bioscience and Bioresources, CNR, Naples, Italy.Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA. Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy. Institute of Bioscience and Bioresources, CNR, Naples, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26540573

Citation

Capasso, Stefania, et al. "Changes in Autophagy, Proteasome Activity and Metabolism to Determine a Specific Signature for Acute and Chronic Senescent Mesenchymal Stromal Cells." Oncotarget, vol. 6, no. 37, 2015, pp. 39457-68.
Capasso S, Alessio N, Squillaro T, et al. Changes in autophagy, proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells. Oncotarget. 2015;6(37):39457-68.
Capasso, S., Alessio, N., Squillaro, T., Di Bernardo, G., Melone, M. A., Cipollaro, M., ... Galderisi, U. (2015). Changes in autophagy, proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells. Oncotarget, 6(37), pp. 39457-68. doi:10.18632/oncotarget.6277.
Capasso S, et al. Changes in Autophagy, Proteasome Activity and Metabolism to Determine a Specific Signature for Acute and Chronic Senescent Mesenchymal Stromal Cells. Oncotarget. 2015 Nov 24;6(37):39457-68. PubMed PMID: 26540573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in autophagy, proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells. AU - Capasso,Stefania, AU - Alessio,Nicola, AU - Squillaro,Tiziana, AU - Di Bernardo,Giovanni, AU - Melone,Mariarosa A, AU - Cipollaro,Marilena, AU - Peluso,Gianfranco, AU - Galderisi,Umberto, PY - 2015/09/10/received PY - 2015/10/02/accepted PY - 2015/11/6/entrez PY - 2015/11/6/pubmed PY - 2016/9/22/medline KW - Gerotarget KW - autophagy KW - mesenchymal stem cells KW - metabolism KW - proteasome KW - senescence SP - 39457 EP - 68 JF - Oncotarget JO - Oncotarget VL - 6 IS - 37 N2 - A sharp definition of what a senescent cell is still lacking since we do not have in depth understanding of mechanisms that induce cellular senescence. In addition, senescent cells are heterogeneous, in that not all of them express the same genes and present the same phenotype. To further clarify the classification of senescent cells, hints may be derived by the study of cellular metabolism, autophagy and proteasome activity. In this scenario, we decided to study these biological features in senescence of Mesenchymal Stromal Cells (MSC). These cells contain a subpopulation of stem cells that are able to differentiate in mesodermal derivatives (adipocytes, chondrocytes, osteocytes). In addition, they can also contribute to the homeostatic maintenance of many organs, hence, their senescence could be very deleterious for human body functions. We induced MSC senescence by oxidative stress, doxorubicin treatment, X-ray irradiation and replicative exhaustion. The first three are considered inducers of acute senescence while extensive proliferation triggers replicative senescence also named as chronic senescence. In all conditions, but replicative and high IR dose senescence, we detected a reduction of the autophagic flux, while proteasome activity was impaired in peroxide-treated and irradiated cells. Differences were observed also in metabolic status. In general, all senescent cells evidenced metabolic inflexibility and prefer to use glucose as energy fuel. Irradiated cells with low dose of X-ray and replicative senescent cells show a residual capacity to use fatty acids and glutamine as alternative fuels, respectively. Our study may be useful to discriminate among different senescent phenotypes. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/26540573/Changes_in_autophagy_proteasome_activity_and_metabolism_to_determine_a_specific_signature_for_acute_and_chronic_senescent_mesenchymal_stromal_cells_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=6277 DB - PRIME DP - Unbound Medicine ER -