Cellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.

H-Ras oncogene requires deregulation of additional oncogenes or inactivation of tumor suppressor proteins to increase cell proliferation rate and transform cells. In fact, the expression of the constitutively activated H-RasV12 induces cell growth arrest and premature senescence, which act like barr...

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Autores principales:	Tatiana Armeni, Luisa Ercolani, Lorena Urbanelli, Alessandro Magini, Francesca Magherini, Armanda Pugnaloni, Francesco Piva, Alessandra Modesti, Carla Emiliani, Giovanni Principato
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a46c62e317d44a6f995b297a448da801
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spelling	oai:doaj.org-article:a46c62e317d44a6f995b297a448da8012021-11-18T08:04:18ZCellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.1932-620310.1371/journal.pone.0052151https://doaj.org/article/a46c62e317d44a6f995b297a448da8012012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284910/?tool=EBIhttps://doaj.org/toc/1932-6203H-Ras oncogene requires deregulation of additional oncogenes or inactivation of tumor suppressor proteins to increase cell proliferation rate and transform cells. In fact, the expression of the constitutively activated H-RasV12 induces cell growth arrest and premature senescence, which act like barriers in pre-neoplastic lesions. In our experimental model, human fibroblasts transfected with H-RasV12 show a dramatic modification of morphology. H-RasV12 expressing cells also show premature senescence followed by cell death, induced by autophagy and apoptosis. In this context, we provide evidence that in H-RasV12 expressing cells, the premature senescence is associated with cellular redox imbalance as well as with altered post-translation protein modification. In particular, redox imbalance is due to a strong reduction of total antioxidant capacity, and significant decrease of glutathione level. As the reversible addition of glutathione to cysteinyl residues of proteins is an important post-translational regulative modification, we investigated S-glutathionylation in cells expressing active H-Ras. In this contest we observed different S-glutathionylation patterns in control and H-RasV12 expressing cells. Particularly, the GAPDH enzyme showed S-glutathionylation increase and significant enzyme activity depletion in H-Ras V12 cells. In conclusion, we proposed that antioxidant defense reduction, glutathione depletion and subsequent modification of S-glutathionylation of target proteins contribute to arrest cell growth, leading to death of fibroblasts expressing constitutively active H-Ras oncogene, thus acting as oncogenic barriers that obstacle the progression of cell transformation.Tatiana ArmeniLuisa ErcolaniLorena UrbanelliAlessandro MaginiFrancesca MagheriniArmanda PugnaloniFrancesco PivaAlessandra ModestiCarla EmilianiGiovanni PrincipatoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e52151 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tatiana Armeni Luisa Ercolani Lorena Urbanelli Alessandro Magini Francesca Magherini Armanda Pugnaloni Francesco Piva Alessandra Modesti Carla Emiliani Giovanni Principato Cellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.
description	H-Ras oncogene requires deregulation of additional oncogenes or inactivation of tumor suppressor proteins to increase cell proliferation rate and transform cells. In fact, the expression of the constitutively activated H-RasV12 induces cell growth arrest and premature senescence, which act like barriers in pre-neoplastic lesions. In our experimental model, human fibroblasts transfected with H-RasV12 show a dramatic modification of morphology. H-RasV12 expressing cells also show premature senescence followed by cell death, induced by autophagy and apoptosis. In this context, we provide evidence that in H-RasV12 expressing cells, the premature senescence is associated with cellular redox imbalance as well as with altered post-translation protein modification. In particular, redox imbalance is due to a strong reduction of total antioxidant capacity, and significant decrease of glutathione level. As the reversible addition of glutathione to cysteinyl residues of proteins is an important post-translational regulative modification, we investigated S-glutathionylation in cells expressing active H-Ras. In this contest we observed different S-glutathionylation patterns in control and H-RasV12 expressing cells. Particularly, the GAPDH enzyme showed S-glutathionylation increase and significant enzyme activity depletion in H-Ras V12 cells. In conclusion, we proposed that antioxidant defense reduction, glutathione depletion and subsequent modification of S-glutathionylation of target proteins contribute to arrest cell growth, leading to death of fibroblasts expressing constitutively active H-Ras oncogene, thus acting as oncogenic barriers that obstacle the progression of cell transformation.
format	article
author	Tatiana Armeni Luisa Ercolani Lorena Urbanelli Alessandro Magini Francesca Magherini Armanda Pugnaloni Francesco Piva Alessandra Modesti Carla Emiliani Giovanni Principato
author_facet	Tatiana Armeni Luisa Ercolani Lorena Urbanelli Alessandro Magini Francesca Magherini Armanda Pugnaloni Francesco Piva Alessandra Modesti Carla Emiliani Giovanni Principato
author_sort	Tatiana Armeni
title	Cellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.
title_short	Cellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.
title_full	Cellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.
title_fullStr	Cellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.
title_full_unstemmed	Cellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.
title_sort	cellular redox imbalance and changes of protein s-glutathionylation patterns are associated with senescence induced by oncogenic h-ras.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a46c62e317d44a6f995b297a448da801
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Cellular redox imbalance and changes of protein S-glutathionylation patterns are associated with senescence induced by oncogenic H-ras.

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