The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia

Molecular and Cellular Therapies ◽

10.13052/s40591-016-0047-9 ◽

2016 ◽

Author(s):

Lilian Enriquez-barreto ◽

Miguel Morales

Keyword(s):

Signaling Pathway ◽

Single Gene ◽

Gene Mutations ◽

Pi3k Pathway ◽

Synaptic Function ◽

Pi3k Signaling ◽

Gene Markers ◽

High Prevalence ◽

Synaptic Formation ◽

Pi3k Signaling Pathway

This review is focused in PI3K’s involvement in two widespread mental disorders: Autism and Schizophrenia. A largebody of evidence points to synaptic dysfunction as a cause of these diseases, either during the initial phases ofbrain synaptic circuit’s development or later modulating synaptic function and plasticity. Autism related disordersand Schizophrenia are complex genetic conditions in which the identification of gene markers has proved difficult,although the existence of single-gene mutations with a high prevalence in both diseases offers insight into the roleof the PI3K signaling pathway. In the brain, components of the PI3K pathway regulate synaptic formation and plasticity;thus, disruption of this pathway leads to synapse dysfunction and pathological behaviors. Here, we recapitulate recentevidences that demonstrate the imbalance of several PI3K elements as leading causes of Autism and Schizophrenia,together with the plausible new pharmacological paths targeting this signaling pathway.

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BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells

Open Life Sciences ◽

10.1515/biol-2020-0054 ◽

2020 ◽

Vol 15 (1) ◽

pp. 501-510

Author(s):

Bin Ma ◽

Wenjia Guo ◽

Meihui Shan ◽

Nan Zhang ◽

Binlin Ma ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Nuclear Localization ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Pi3k Pathway ◽

Pi3k Signaling ◽

T47d Cells ◽

Pi3k Signaling Pathway ◽

Hormone Sensitive

AbstractThis study is to investigate the effect of the PI3K/Akt signaling pathway on the regulation of BRCA1 subcellular localization in triple-negative breast cancer (TNBC) MDA-MB-231 cells and hormone-sensitive T47D cells. We found that heregulin-activated T47D cells showed more nuclear localization of BRCA1, but BRCA1 nuclear localization decreased after the inhibition of the PI3K signaling pathway. In MDA-MB-231 cells, activation or inhibition of the PI3K signaling pathway did not significantly affect cell apoptosis and BRCA1 nuclear translocation (P > 0.05). However, in T47D cells, the activation of the PI3K pathway significantly increased cell apoptosis (P < 0.05). In the heregulin-activated MDA-MB-231 and T47D cells, the phosphorylation of Akt and BRCA1 was significantly increased (P < 0.05), while that was significantly reduced after PI3K pathway inhibition (P < 0.05). The changing trends of the mRNA levels of Akt and BRCA1 in MDA-MB-231 and T47D cells after PI3K pathway activation or inhibition were consistent with the trends of their proteins. In both MDA-MB-231 and T47D cells, BRCA1 phosphorylation is regulated by the PI3K signaling pathway, but the nuclear localization of BRCA1 is different in these two cell lines. Moreover, the apoptosis rates of these two cell lines are different.

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Short-term effects of triiodothyronine on thyroid hormone receptor alpha by PI3K pathway in adipocytes, 3T3-L1

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/0004-2730000003295 ◽

2014 ◽

Vol 58 (8) ◽

pp. 833-837 ◽

Cited By ~ 2

Author(s):

Miriane de Oliveira ◽

Regiane Marques Castro Olimpio ◽

Maria Teresa De Sibio ◽

Fernanda Cristina Fontes Moretto ◽

Renata de Azevedo Mello Luvizotto ◽

...

Keyword(s):

Thyroid Hormone ◽

Mrna Expression ◽

Signaling Pathway ◽

Thyroid Hormone Receptor ◽

Pi3k Pathway ◽

Control Group ◽

Pi3k Signaling ◽

Pi3k Inhibitor Ly294002 ◽

Receptor Alpha ◽

Pi3k Signaling Pathway

Objective The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of TH receptor alpha (TRα) mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. Materials and methods: It was examined the involvement of PI3K pathway in mediating T3 effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI =100 nM) T3 doses during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey’s test was used at 5% significance level. Results T3 increased TRα mRNA expression in P (1.91±0.13, p<0.001), SI (2.14±0.44, p<0.001) compared to C group (1±0.08). This increase was completely abrogated by LY294002 in P (0.53±0.03, p<0.001) and SI (0.31±0.03, p<0.001). To examine whether TRα is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). The presence of CHX completely abrogated levels TRα mRNA in P (1.15±0.05, p>0.001) and SI (0.99±0.15, p>0.001), induced by T3. Conclusion These results demonstrate that the activation of the PI3K signaling pathway has a role in T3-mediated indirect TRα gene expression in 3T3-L1 adipocytes.

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The Role of miRNAs in PI3K Signaling Pathway in Blood Malignancies: A Review Article

Journal of Zabol Medical School ◽

10.18502/jzms.v4i1.6760 ◽

2021 ◽

Author(s):

Haniyeh Gaffari-Nazari ◽

Samira Karami ◽

Leila Noorazar ◽

Sayeh Parkhideh ◽

Elham Roshandel ◽

...

Keyword(s):

Treatment Failure ◽

Signaling Pathway ◽

Intracellular Signaling ◽

Pi3k Pathway ◽

Pi3k Signaling ◽

Laboratory Findings ◽

A Cell ◽

Pi3k Signaling Pathway ◽

Relationship Of

Background: The PI3K/Akt/mTOR signaling pathway is one of the most important intracellular signaling pathways by regulating the cell cycle process. The direct relationship of this pathway with important mechanisms such as cell quiescence, longevity, and proliferation has been established. The overactive PI3K pathway with decreased and increased apoptosis and cell proliferation respectively is involved in pathogenesis of many cancers, including blood malignancies such as leukemia. Methods: Laboratory findings have shown that different factors, such as miRNAs, play a role in regulating PI3K signaling pathway. These molecules can alter the fate of a cell by interfering in suppression/overexpression of mRNA, transcription factors or stimulating the transcription of some genes. In this article, we reviewed the role of miRNAs in regulating the PI3K/Akt/mTOR pathway and its effect on leukemic progression and treatment failure. Conclusion: At present, miRNAs are known to be one of the causes of treatment failure and relapse in cancers.

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Quercetin Prevents Primordial Follicle Loss via Suppression of PI3K/Akt/Foxo3a Pathway Activation in Cyclophosphamide - Treated Mouse

10.21203/rs.3.rs-136230/v1 ◽

2020 ◽

Author(s):

Jianghui Li ◽

Hui Long ◽

Yanyan Cong ◽

Hongyuan Gao ◽

Qifeng Lyu ◽

...

Keyword(s):

Signaling Pathway ◽

Survival Rates ◽

Primordial Follicle ◽

Pi3k Pathway ◽

Pi3k Signaling ◽

Primordial Follicles ◽

Pathway Activation ◽

Pi3k Signaling Pathway ◽

Induced Apoptosis ◽

Immunohistochemistry Stain

Abstract Background: Chemotherapy improves survival rates but often causes some adverse effects associated with ovarian damage, characterized by a decreased of primordial follicle stockpiles. Recent studies reveal that chemotherapy may stimulate the PI3K signaling pathway, who has roles in manipulating the dormancy and activation of mammalian primordial follicles, resulting in accelerated primordial follicles activation followed by the loss of ovarian reserve. As an inhibitor of PI3K pathway, whether quercetin has protective properties against chemotherapy - induced follicle loss in mice is worth to be explored.Methods: The effects of quercetin on the mouse model of cyclophosphamide-induced ovarian dysfunction were investigated. Paraffin sections of mouse ovary were stained with hematoxylin and eosin for differential follicles count and TUNEL assay for apoptosis detection. Immunohistochemistry stain with ki67 and Foxo3a were used to evaluate the activation of primordial follicles. The function of PI3K signaling pathway were assessed via the western blot of ovary.Results: Quercetin cotreatment rescued the reduction number of dormant primordial follicles induced by cyclophosphamide. Moreover, analysis of the PI3K/Akt/Foxo3a pathway demonstrated that quercetin co - administration decreased phosphorylation of proteins that stimulate follicle activation in ovary induced by cyclophosphamide. Meanwhile, Quercetin prevents cyclophosphamide - induced apoptosis in early growing follicles and early antral follicles, maintaining AMH level secreted by these follicles, preserving the quiescence of the primordial follicle pool, characterized by the intranuclear staining of Foxo3a in primordial follicle. Conclusions: Quercetin attenuates cyclophosphamide - induced follicle loss by preventing the phosphorylation of PI3K/Akt/Foxo3a pathway members and maintaining AMH level secreted by growing follicles.

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Quercetin Prevents Primordial Follicle Loss via Suppression of PI3K/Akt/Foxo3a Pathway Activation in Cyclophosphamide - Treated Mouse

10.21203/rs.3.rs-108112/v1 ◽

2020 ◽

Author(s):

Sha Yu ◽

Jianghui Li ◽

Hui Long ◽

Yanyan Cong ◽

Hongyuan Gao ◽

...

Keyword(s):

Signaling Pathway ◽

Survival Rates ◽

Primordial Follicle ◽

Pi3k Pathway ◽

Pi3k Signaling ◽

Primordial Follicles ◽

Pathway Activation ◽

Pi3k Signaling Pathway ◽

Induced Apoptosis ◽

Immunohistochemistry Stain

Abstract Background: Chemotherapy improves survival rates but often causes some adverse effects associated with ovarian damage, characterized by a decreased of primordial follicle stockpiles. Recent studies reveal that chemotherapy may stimulate the PI3K signaling pathway, who has roles in manipulating the dormancy and activation of mammalian primordial follicles, resulting in accelerated primordial follicles activation followed by the loss of ovarian reserve. As an inhibitor of PI3K pathway, whether quercetin has protective properties against chemotherapy - induced follicle loss in mice is worth to be explored.Methods：The effects of quercetin on the mouse model of cyclophosphamide-induced ovarian dysfunction were investigated. Paraffin sections of mouse ovary were stained with hematoxylin and eosin for differential follicles count and TUNEL assay for apoptosis detection. Immunohistochemistry stain with ki67 and Foxo3a were used to evaluate the activation of primordial follicles. The function of PI3K signaling pathway were assessed via the western blot of ovary.Results: Quercetin cotreatment rescued the reduction number of dormant primordial follicles induced by cyclophosphamide. Moreover, analysis of the PI3K/Akt/Foxo3a pathway demonstrated that quercetin co - administration decreased phosphorylation of proteins that stimulate follicle activation in ovary induced by cyclophosphamide. Meanwhile, Quercetin prevents cyclophosphamide - induced apoptosis in early growing follicles and early antral follicles, maintaining AMH level secreted by these follicles, preserving the quiescence of the primordial follicle pool, characterized by the intranuclear staining of Foxo3a in primordial follicle. Conclusions: Quercetin attenuates cyclophosphamide - induced follicle loss by preventing the phosphorylation of PI3K/Akt/Foxo3a pathway members and maintaining AMH level secreted by growing follicles.

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The PI3K signaling pathway mediates the biological effects of leptin

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302010000700002 ◽

2010 ◽

Vol 54 (7) ◽

pp. 591-602 ◽

Cited By ~ 31

Author(s):

Jose Donato Jr. ◽

Renata Frazão ◽

Carol Fuzeti Elias

Keyword(s):

Food Intake ◽

Signaling Pathways ◽

Signaling Pathway ◽

Intracellular Signaling ◽

Leptin Receptor ◽

Biological Effects ◽

Pi3k Pathway ◽

Pi3k Signaling ◽

Electrophysiological Properties ◽

Pi3k Signaling Pathway

The activation of the leptin receptor recruits several intracellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway. While some of the leptin-induced signaling pathways, such as the JAK2/STAT3 pathway, induce cellular responses primarily through changes in gene expression, the PI3K pathway affects cellular properties more rapidly, through post-translational changes such as protein phosphorylation. Accordingly, several studies have shown that the PI3K pathway is required for the acute effects of leptin, such as a leptin-induced decrease in food intake. Leptin signaling through PI3K also affects the electrophysiological properties of neurons, including changes in their membrane potential and firing rates. In this review, we summarize the recent advances in our understanding of the role played by the PI3K signaling pathway in controlling food intake and energy balance. In particular, we focus on the importance of the PI3K signaling pathway as a mediator of the effects of leptin on hypothalamic neurons.

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