Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression

Ávila-Rodriguez, Marco; Garcia-Segura, Luis Miguel; Hidalgo-Lanussa, Oscar; Báez, Eliana; González, Janneth; Barreto, George E.

doi:10.1016/j.mce.2016.05.024

Cited by 64 publications

(58 citation statements)

References 49 publications

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“…All the reactions involved in the conversion of extracellular glutamate, glycine, cysteine and glucose to extracellular glutamine, glycine, serine-D, reduced glutathione, lactate, and ATP were added, as they are essential for the normal astrocytic metabolism (Barreto et al, 2011;Souza et al, 2019). Exchange reactions were limited to components of the Dulbecco's Modified Eagle Medium (DMEM) as an input, and the gliotransmitters, glutamine, D-serine, ATP and glutamate, reduced glutathione, lactate, glucose, nitric oxide, prostaglandins and leukotrienes as output, in accordance with previous experimental studies from our group (Avila-Rodriguez et al, 2016;Cabezas et al, 2018;González-Giraldo et al, 2019). Finally, we developed the R Package "MinVal" to validate the syntax of the model, the mass-charge and the creation of SBML files (Osorio et al, 2017).…”

Section: Tissue Specific Model Constructionsupporting

confidence: 53%

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

et al. 2020

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Inflammation is a complex biological response to injuries, metabolic disorders or infections. In the brain, astrocytes play an important role in the inflammatory processes during neurodegenerative diseases. Recent studies have shown that the increase of free saturated fatty acids such as palmitic acid produces a metabolic inflammatory response in astrocytes generally associated with damaging mechanisms such as oxidative stress, endoplasmic reticulum stress, and autophagic defects. In this aspect, the synthetic neurosteroid tibolone has shown to exert protective functions against inflammation in neuronal experimental models without the tumorigenic effects exerted by sexual hormones such as estradiol and progesterone. However, there is little information regarding the specific mechanisms of tibolone in astrocytes during inflammatory insults. In the present study, we performed a genome-scale metabolic reconstruction of astrocytes that was used to study astrocytic response during an inflammatory insult by palmitate through Flux Balance Analysis methods and data mining. In this aspect, we assessed the metabolic fluxes of human astrocytes under three different scenarios: healthy (normal conditions), induced inflammation by palmitate, and tibolone treatment under palmitate inflammation. Our results suggest that tibolone reduces the L-glutamate-mediated neurotoxicity in astrocytes through the modulation of several metabolic pathways involved in glutamate uptake. We also identified a set of reactions associated with the protective effects of tibolone, including the upregulation of taurine metabolism, gluconeogenesis, cPPAR and the modulation of calcium signaling pathways. In conclusion, the different scenarios studied in our model allowed us to identify several metabolic fluxes perturbed under an inflammatory response and the protective mechanisms exerted by tibolone.

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Section: Tissue Specific Model Constructionsupporting

confidence: 53%

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

et al. 2020

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“…Moreover, recent study has shown that Ngb silencing in human T98G astroglial cells reduced cell viability and prevented the protective action of tibolone against glucose deprivation‐provoked mitochondria dysfunction cell death apoptosis (Avila‐Rodriguez et al . ).…”

Section: Discussionmentioning

confidence: 97%

Neuroglobin protects astroglial cells from hydrogen peroxide‐induced oxidative stress and apoptotic cell death

Amri

Ghouili

Amri

et al. 2016

Journal of Neurochemistry

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Oxidative stress, resulting from accumulation of reactive oxygen species, plays a critical role in astroglial cell death occurring in diverse neuropathological conditions. Numerous studies indicate that neuroglobin (Ngb) promotes neuron survival, but nothing is known regarding the action of Ngb in astroglial cell survival. Thus, the purpose of this study was to investigate the potential glioprotective effect of Ngb on hydrogen peroxide (H 2 O 2 )-induced oxidative stress and apoptosis in cultured mouse astrocytes.

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“…Since glucose withdrawal can induce mitochondrial dysfunction and oxidative stress (Avila-Rodriguez et al, 2014;Avila-Rodriguez et al, 2016;Toro-Urrego et al, 2016), we evaluated whether raloxifene (1 µM) was able to regulate mitochondrial function in BSS0 cells. As shown in Figure 2, BSS0 cells had increased superoxide (Figure 2a; p < 0.0001), hydroxyl, and peroxyl levels when compared with BSS5 cells (Figure 2b; p < 0.0001).…”

Section: Resultsmentioning

confidence: 99%

“…In this study, a metabolic insult (GD) was induced in an in vitro astrocytic model, T98G, and the effects of pretreatment with raloxifene were tested. Previous studies indicated that estradiol, when added before GD, induced protective actions by increasing cell viability, preserving mitochondrial membrane potential, and reducing the production of ROS (Avila-Rodriguez et al, 2014;Avila-Rodriguez et al, 2016;Karki, Smith et al, 2014;Toro-Urrego et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Raloxifene attenuates oxidative stress and preserves mitochondrial function in astrocytic cells upon glucose deprivation

Vesga-Jiménez

Hidalgo-Lanussa

Baez‐Jurado

et al. 2018

Journal Cellular Physiology

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Oxidative stress and mitochondrial dysfunction induced by metabolic insults are both hallmarks of various neurological disorders, whereby neuronal cells are severely affected by decreased glucose supply to the brain. Likely injured, astrocytes are important for neuronal homeostasis and therapeutic strategies should be directed towards improving astrocytic functions to improve brain's outcome. In the present study, we aimed to assess the actions of raloxifene, a selective estrogen receptor modulator in astrocytic cells under glucose deprivation. Our findings indicated that pretreatment with 1 µM raloxifene results in an increase in cell viability and attenuated nuclei fragmentation. Raloxifene's actions also rely on the reduction of oxidative stress and preservation of mitochondrial function in glucose‐deprived astrocytic cells, suggesting the possible direct effects of this compound on mitochondria. In conclusion, our results demonstrate that raloxifene's protective actions might be mediated in part by astrocytes in the setting of a metabolic insult.

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Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression

Cited by 64 publications

References 49 publications

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

Neuroglobin protects astroglial cells from hydrogen peroxide‐induced oxidative stress and apoptotic cell death

Raloxifene attenuates oxidative stress and preserves mitochondrial function in astrocytic cells upon glucose deprivation

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