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Antioxidants 2017, 6(3), 48; doi:10.3390/antiox6030048

Early and Late Induction of KRAS and HRAS Proto-Oncogenes by Reactive Oxygen Species in Primary Astrocytes

1
Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, Cassino 03043, Italy
2
Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, Campobasso 86100, Italy
*
Author to whom correspondence should be addressed.
Received: 1 June 2017 / Revised: 17 June 2017 / Accepted: 19 June 2017 / Published: 29 June 2017
(This article belongs to the Special Issue Astrocyte Antioxidant Systems)
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Abstract

Astrocytes, one of the predominant types of glial cells, function as both supportive and metabolic cells for the brain. Among mammalian tissues, the highest levels of p21Ras protein are detected in the brain. Here, we investigated the expression of KRAS and HRAS proto-oncogenes in primary astrocytes following acute oxidative stimulation. Reactive oxygen species (ROS) changed the expression of proto-oncogenes at both transcriptional and translational levels. De novo protein synthesis analysis measured approximate values of proteins half-life, ranging from 1–4 h, of the different H- and K- isoforms by western blot analysis. Quantitative gene expression analysis of KRAS and HRAS revealed an unexpected short-term induction of KRAS mRNA in primary astrocytes in response to acute stimulation. Indeed, cultured astrocytes responded to proteasomal inhibition by preventing the reduction of c-K-Ras. A fraction of K-Ras protein accumulated in the presence of ROS and cycloheximide, while a substantial proportion was continuously synthesized. These data indicate that ROS regulate in a complementary fashion p21Ras isoforms in primary astrocytes: K-Ras is rapidly and transiently induced by post-translational and post-transcriptional mechanisms, while H-Ras is stably induced by mRNA accumulation. We suggest that K-Ras and H-Ras are ROS sensors that adapt cells to metabolic needs and oxidative stress. View Full-Text
Keywords: p21Ras; KRAS; HRAS; astrocytes; reactive oxygen species p21Ras; KRAS; HRAS; astrocytes; reactive oxygen species
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Messina, S.; Di Zazzo, E.; Moncharmont, B. Early and Late Induction of KRAS and HRAS Proto-Oncogenes by Reactive Oxygen Species in Primary Astrocytes. Antioxidants 2017, 6, 48.

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