Guanosine protects SH-SY5Y cells against β-amyloid-induced apoptosis

Pettifer, Kathleen M.; Kleywegt, Sonya; Bau, Christian; Ramsbottom, James D.; Vertes, Eva; Ciccarelli, Renata; Caciagli, Francesco; Werstiuk, Eva S.; Rathbone, Michel P.

doi:10.1097/00001756-200404090-00019

Cited by 46 publications

(54 citation statements)

References 22 publications

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“…As reported previously (Li et al, 1996;Luetjens et al, 2001;Olivieri et al, 2001;Wei et al, 2002;Pettifer et al, 2004;Arias et al, 2005), A␤ 25-35 peptide induced a strong loss of cell viability in SH-SY5Y cells with an approximate EC 50 of 10 M at 24 h (Fig. 1B).…”

Section: Resultssupporting

confidence: 87%

Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-β Peptide

Gomez‐Brouchet¹,

Pchejetski²,

Brizuela³

et al. 2007

Mol Pharmacol

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We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the ceramide/sphingosine 1-phosphate (S1P) biostat, in the regulation of death and survival of SH-SY5Y neuroblastoma cells in response to amyloid ␤ (A␤) peptide (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Upon incubation with A␤, SH-SY5Y cells displayed a marked down-regulation of SphK1 activity coupled with an increase in the ceramide/S1P ratio followed by cell death. This mechanism was redox-sensitive; N-acetylcysteine totally abrogated the down-regulation of SphK1 activity and strongly inhibited A␤-induced cell death. SphK1 overexpression impaired the cytotoxicity of A␤, whereas SphK1 silencing by RNA interference mimicked A␤-induced cell death, thereby establishing a critical role for SphK1. We further demonstrated that SphK1 could mediate the well established cytoprotective action of insulin-like growth factor (IGF-I) against A␤ toxicity. A dominant-negative form of SphK1 or its pharmacological inhibition not only abrogated IGF-I-triggered stimulation of SphK1 but also hampered IGF-I protective effect. Similarly to IGF-I, the neuroprotective action of TGF-␤1 was also dependent on SphK1 activity; activation of SphK1 as well as cell survival were impeded by a dominant-negative form of SphK1. Taken together, these results provide the first illustration of SphK1 role as a critical regulator of death and survival of A␤-treated cells.

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Section: Resultssupporting

confidence: 87%

Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-β Peptide

Gomez‐Brouchet¹,

Pchejetski²,

Brizuela³

et al. 2007

Mol Pharmacol

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“…The MAPK signaling pathway has also been described as a modulator of glutamate uptake [70,71]. Because guanosine modulates this pathway [14], we investigated whether the protective effect of guanosine on glutamate uptake was also dependent of p38 MAPK and ERK. Coincubation with the p38 MAPK inhibitor (SB203580-5 μM, Fig.…”

Section: Resultsmentioning

confidence: 98%

“…Guanosine is released from astrocytes and confers neuroprotective effects in several in vivo and in vitro studies [3,[6][7][8][9][10][11]. Guanosine can effectively protect cells against hypoxia [12,13], cytotoxicity induced by the β-amyloid peptide [14], chronic cerebral hypoperfusion [15], ischemic insults [16][17][18], and other glutamatergic excitotoxic damage, such as seizures that are induced by quinolinic acid [3,9,19,20] and methylmercury-induced oxidative stress [21]. Although there is increasing evidence showing the neuroprotective effects of guanosine on models of neurotoxicity, its mechanisms are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Gliopreventive effects of guanosine against glucose deprivation in vitro

Quincozes‐Santos

Bobermin

Souza

et al. 2013

Purinergic Signalling

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Guanosine, a guanine-based purine, is recognized as an extracellular signaling molecule that is released from astrocytes and confers neuroprotective effects in several in vivo and in vitro studies. Astrocytes regulate glucose metabolism, glutamate transport, and defense mechanism against oxidative stress. C6 astroglial cells are widely used as an astrocyte-like cell line to study the astrocytic function and signaling pathways. Our previous studies showed that guanosine modulates the glutamate uptake activity, thus avoiding glutamatergic excitotoxicity and protecting neural cells. The goal of this study was to determine the gliopreventive effects of guanosine against glucose deprivation in vitro in cultured C6 cells. Glucose deprivation induced cytotoxicity, an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and lipid peroxidation as well as affected the metabolism of glutamate, which may impair important astrocytic functions. Guanosine prevented glucose deprivation-induced toxicity in C6 cells by modulating oxidative and nitrosative stress and glial responses, such as the glutamate uptake, the glutamine synthetase activity, and the glutathione levels. Glucose deprivation decreased the level of EAAC1, the main glutamate transporter present in C6 cells. Guanosine also prevented this effect, most likely through PKC, PI3K, p38 MAPK, and ERK signaling pathways. Taken together, these results show that guanosine may represent an important mechanism for protection of glial cells against glucose deprivation. Additionally, this study contributes to a more thorough understanding of the glial-and redox-related protective properties of guanosine in astroglial cells.

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“…Recently, Guo has been found to protect against beta-amyloid-induced apoptosis (Pettifer et al 2004 ) . This effect appeared to be mediated by the antiapoptotic properties of Guo (Di Iorio et al 2004 ) .…”

Section: Dementiamentioning

confidence: 99%

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

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Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer's disease, Huntington's disease, and Parkinson's disease. Consequently, increasing attention is now being given to the speci fi c role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner.Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies.

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Guanosine protects SH-SY5Y cells against β-amyloid-induced apoptosis

Cited by 46 publications

References 22 publications

Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-β Peptide

Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-β Peptide

Gliopreventive effects of guanosine against glucose deprivation in vitro

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

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