Growth Arrest Specific 1 (GAS1) Is Abundantly Expressed in the Adult Mouse Central Nervous System

Abstract

Growth arrest specific 1 (GAS1) is a pleiotropic protein that induces apoptosis and cell arrest in different tumors, but it is also involved in the development of the nervous system and other tissues and organs. This dual ability is likely caused by its capacity to interact both by inhibiting the intracellular signaling cascade induced by glial cell-line derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. The presence of GAS1 mRNA has been described in adult mouse brain, and here we corroborated this observation. We then proceeded to determine the distribution of the protein in the adult central nervous system (CNS). We detected, by western blot analysis, expression of GAS1 in olfactory bulb, caudate-putamen, cerebral cortex, hippocampus, mesencephalon, medulla oblongata, cerebellum, and cervical spinal cord. To more carefully map the expression of GAS1, we performed double-label immunohistochemistry and noticed expression of GAS1 in neurons in all brain areas examined. We also observed expression of GAS1 in astroglial cells, albeit the pattern of expression was more restricted than that seen in neurons. Briefly, in the present article, we report the widespread distribution and cellular localization of the GAS1 native protein in adult mammalian CNS.

GAS1 is present in the cerebrospinal fluid and is expressed in the choroid plexus of the adult rat

“…Furthermore, we confirmed the levels of GAS1 in the rat brain at different ages by ELISA. The expression of GAS1 in rat brain, from postnatal 0 to the adult is similar to that previously described in mouse (Zarco et al 2013;Estudillo et al 2016).…”

“…To confirm whether the anti-mouse GAS1 antibody recognizes the same protein in the rat, we performed western blot and ELISA assays using whole rat brain extracts of P0, P7 day-old and adult rats since GAS1 is expressed at the same ages in the mouse (Zarco et al 2013;Estudillo et al 2016). We observed a protein band corresponding to GAS1 (37 kDa) in all brain extracts of the rat as confirmed by the positive control, NIH/3T3 mouse cells at confluence (Fig.…”

Annexin A1, Annexin A2, and Dyrk 1B are upregulated during GAS1‐induced cell cycle arrest

“…In contrast, it has been reported that Gas1 may also act as a positive regulator of cell proliferation in mouse cerebellum during development (Liu et al, ); and also is expressed in different types of progenitor cells (Izzi et al, ; Kann et al, ), demonstrating the significant role of Gas1 in embryonic development (Lee et al, 2001; Lee & Fan, ; Martinelli & Fan, ). In fact, we have demonstrated that Gas1 is present in progenitor cells during the development of the dentate gyrus and the cortex (Estudillo, Zavala, Perez‐Sanchez, Ayala‐Sarmiento, & Segovia, ) and also in neurons and astroglial cells of adult mouse brain (Zarco et al, ). Finally, these results indicate that Gas1 may act either as a regulator of cell proliferation or as an inducer of cell death in a finely controlled spatio‐temporal manner.…”

Effects of Gas1 on gliomas: a review on current preclinical studies

“…Additionally, we reported that Gas1 is mainly found in neurons and in a more restricted manner in glial cells in different regions of the CNS of adult mice. [97] Furthermore, the expression of Gas1 decreases when neural stem cells are differentiated to a glial phenotype. [98] However, the role of Gas1 in glial cells is unknown in the adult CNS.…”