GSK3β: a plausible mechanism of cognitive and hippocampal changes induced by erythropoietin treatment in mood disorders?

Inkster, Becky; Zai, Gwyneth; Lewis, Gemma; Miskowiak, Kamilla Woznica

doi:10.1038/s41398-018-0270-z

Cited by 23 publications

(18 citation statements)

References 176 publications

(221 reference statements)

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“…Previous studies have identified that GSK-3β can phosphorylate various endogenous substrates, including proteins associated with metabolism and transcription factors. GSK-3β serves an important role in cell growth, development, tumorigenesis and the regulation of glucose homeostasis (99–102). PI3K-dependent Akt is activated by insulin and growth factors that cause GSK-3β N terminal serine phosphorylation to inhibit GSK-3β activity.…”

Section: Pi3k/akt Signaling Pathway and Glycolysismentioning

confidence: 99%

PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review)

et al. 2018

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The purpose of this review is to summarize the research progress of PI3K/Akt signaling pathway in erythropoiesis and glycolysis. Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is activated by numerous genes and leads to protein kinase B (Akt) binding to the cell membrane, with the help of phosphoinositide-dependent kinase, in the PI3K/Akt signal transduction pathway. Threonine and serine phosphorylation contribute to Akt translocation from the cytoplasm to the nucleus and further mediates enzymatic biological effects, including those involved in cell proliferation, apoptosis inhibition, cell migration, vesicle transport and cell cancerous transformation. As a key downstream protein of the PI3K/Akt signaling pathway, hypoxia-inducible factor (HIF)-1 is closely associated with the concentration of oxygen in the environment. Maintaining stable levels of HIF-1 protein is critical under normoxic conditions; however, HIF-1 levels quickly increase under hypoxic conditions. HIF-1α is involved in the acute hypoxic response associated with erythropoietin, whereas HIF-2α is associated with the response to chronic hypoxia. Furthermore, PI3K/Akt can reduce the synthesis of glycogen and increase glycolysis. Inhibition of glycogen synthase kinase 3β activity by phosphorylation of its N-terminal serine increases accumulation of cyclin D1, which promotes the cell cycle and improves cell proliferation through the PI3K/Akt signaling pathway. The PI3K/Akt signaling pathway is closely associated with a variety of enzymatic biological effects and glucose metabolism.

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Section: Pi3k/akt Signaling Pathway and Glycolysismentioning

confidence: 99%

PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review)

et al. 2018

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“…Glycogen synthase kinase 3 beta (GSK3β) is an uncommon protein serine kinase that participates in several cellular signaling pathways and is associated with multiple rewards and motivational disorders (Xu et al, 2011 ; Shi et al, 2014 ; Huang et al, 2015 ; Patel and Woodgett, 2017 ; Inkster et al, 2018 ). The activity of GSK3β in the NAc core mediates the initiation and expression of methamphetamine-induced locomotor sensitization, suggesting that GSK3β may be a potential target for the treatment of psychostimulant addiction.…”

Section: Possible Influencing Factors That Mediate the Comorbidity Ofmentioning

confidence: 99%

The Nucleus Accumbens: A Common Target in the Comorbidity of Depression and Addiction

Nan

2020

Front. Neural Circuits

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The comorbidity of depression and addiction has become a serious public health issue, and the relationship between these two disorders and their potential mechanisms has attracted extensive attention. Numerous studies have suggested that depression and addiction share common mechanisms and anatomical pathways. The nucleus accumbens (NAc) has long been considered a key brain region for regulating many behaviors, especially those related to depression and addiction. In this review article, we focus on the association between addiction and depression, highlighting the potential mediating role of the NAc in this comorbidity via the regulation of changes in the neural circuits and molecular signaling. To clarify the mechanisms underlying this association, we summarize evidence from overlapping reward neurocircuitry, the resemblance of cellular and molecular mechanisms, and common treatments. Understanding the interplay between these disorders should help guide clinical comorbidity prevention and the search for a new target for comorbidity treatment.

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“…Our experiments suggest that EPO could be a pro-inflammatory molecule since it triggers the expression of angiotensin I/II, which may act as an inflammatory agent by enhancing vascular permeability through VEGF. 39 , 103 − 106 Oxygen imbalance condition (1% O 2 ) increased EPO two-fold, whereas nine-fold for VEGF suggesting that EPO-induced angiogenesis signaling through VEGF is amplified under hypoxia. Our data demonstrated that EPO and VEGF expressions are regulated in parallel and they may communicate directly or indirectly through downstream regulators, including STAT3 and JAK2 phosphorylations.…”

Section: Discussionmentioning

confidence: 99%

Dual Switch Mechanism of Erythropoietin as an Antiapoptotic and Pro-Angiogenic Determinant in the Retina

Samson

Sripathi

et al. 2020

ACS Omega

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Constant or intense light degenerates the retina and retinal pigment epithelial cells. Light generates reactive oxygen species and nitric oxide leading to initial reactions of retinal degeneration. Apoptosis is the primary mechanism of abnormal death of photoreceptors, retinal ganglion cells, or retinal pigment epithelium (RPE) in degenerative retinal diseases, including diabetic retinopathy and age-related macular degeneration. The current study evaluated the function of erythropoietin (EPO) on angiogenesis and apoptosis in the retina and RPE under oxidative stress. We determined the pro-angiogenic and antiapoptotic mechanism of EPO under stress conditions using a conditional EPO knockdown model using siRNA, EPO addition, proteomics, immunocytochemistry, and bioinformatic analysis. Our studies verified that EPO protected retinal cells from light-, hypoxia-, hyperoxia-, and hydrogen peroxide-induced apoptosis through caspase inhibition, whereas up-regulated angiogenic reactions through vascular endothelial growth factor (VEGF) and angiotensin pathway. We demonstrated that the EPO expression in the retina and subsequent serine/threonine/tyrosine kinase phosphorylations might be linked to oxidative stress response tightly to determining angiogenesis and apoptosis. Neuroprotective roles of EPO may involve the balance between antiapoptotic and pro-angiogenic signaling molecules, including BCL-xL, c-FOS, caspase-3, nitric oxide, angiotensin, and VEGF receptor. Our data indicate a new therapeutic application of EPO toward retinal degeneration based on the dual roles in apoptosis and angiogenesis at the molecular level under oxidative stress.

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GSK3β: a plausible mechanism of cognitive and hippocampal changes induced by erythropoietin treatment in mood disorders?

Cited by 23 publications

References 176 publications

PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review)

PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review)

The Nucleus Accumbens: A Common Target in the Comorbidity of Depression and Addiction

Dual Switch Mechanism of Erythropoietin as an Antiapoptotic and Pro-Angiogenic Determinant in the Retina

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