Effects of erythropoietin on intracellular calcium concentration of rat primary cortical neurons

Andoh, Tomio; Echigo, Noriyuki; Kamiya, Yoshinori; Hayashi, Michiko; Kudoh, Ichidai; Goto, Takahisa

doi:10.1016/j.brainres.2011.02.077

Cited by 10 publications

(8 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data suggest that EPO-induced SIRT1 activation may activate AKT via PPARγ but not via the mTOR pathway. EPO also reportedly induced Ca 2+ influx in erythroblasts, myoblasts and neurons 36 46 . Our data also demonstrated that EPO-induced AMPK activation was hampered by CaMKK inhibitor treatment but not by LKB1 knockdown ( Fig.…”

Section: Discussionmentioning

confidence: 92%

Erythropoietin alleviates hepatic insulin resistance via PPARγ-dependent AKT activation

Zhang

Hong

et al. 2015

Sci Rep

View full text Add to dashboard Cite

Erythropoietin (EPO) has beneficial effects on glucose metabolism and insulin resistance. However, the mechanism underlying these effects has not yet been elucidated. This study aimed to investigate how EPO affects hepatic glucose metabolism. Here, we report that EPO administration promoted phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation in palmitic acid (PA)-treated HepG2 cells and in the liver of high-fat diet (HFD)-fed mice, whereas adenovirus-mediated silencing of the erythropoietin receptor (EPOR) blocked EPO-induced AKT signalling in HepG2 cells. Importantly, a peroxisome proliferator-activated receptor γ (PPARγ) antagonist and PPARγ small interfering RNA (siRNA) abrogated the EPO-induced increase in p-AKT in HepG2 cells. Lentiviral vector-mediated hepatic PPARγ silencing in HFD-fed C57BL/6 mice impaired EPO-mediated increases in glucose tolerance, insulin sensitivity and hepatic AKT activation. Furthermore, EPO activated the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signalling pathway, and AMPKα and SIRT1 knockdown each attenuated the EPO-induced PPARγ expression and deacetylation and PPARγ-dependent AKT activation in HepG2 cells. In summary, these findings suggest that PPARγ is involved in EPO/EPOR-induced AKT activation, and targeting the PPARγ/AKT pathway via EPO may have therapeutic implications for hepatic insulin resistance and type 2 diabetes.

show abstract

Section: Discussionmentioning

confidence: 92%

Erythropoietin alleviates hepatic insulin resistance via PPARγ-dependent AKT activation

Zhang

Hong

et al. 2015

Sci Rep

View full text Add to dashboard Cite

show abstract

“…It has been widely observed that neurotoxicity is one of the most common signals for synaptic failure, and these events are associated to changes in protein levels of the synaptic machinery. For example, changes in levels of presynaptic proteins such as synaptic vessel 2 proteins (SV2) affect neurotransmitter release and could be correlated with the decrease in spontaneous calcium transients which reflects a post-synaptic response that could be a result of the toxicity induced by A β 40 [33]. To test this hypothesis, we used an immunocytochemistry approach to measure the immunoreactivity of SV2 proteins (Fig.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective effects of EpoL against oxidative stress induced by soluble oligomers of Aβ peptide

et al. 2019

View full text Add to dashboard Cite

Erythropoietin is a glycoproteic hormone that regulates hematopoiesis by acting on its specific receptor (EpoR). The expression of EpoR in the central nervous system (CNS) suggests a role for this hormone in the brain. Recently, we developed a new Epo variant without hematopoietic activity called EpoL, which showed marked neuroprotective effects against oxidative stress in brain ischemia related models. In this study, we have evaluated the neuroprotective effects of EpoL against oxidative stress induced by chronic treatment with A β . Our results show that EpoL was neuroprotective against A β -induced toxicity by a mechanism that implicates EpoR, reduction in reactive oxygen species, and reduction in astrogliosis. Furthermore, EpoL treatment improved calcium handling and SV2 levels. Interestingly, the neuroprotective effect of EpoL against oxidative stress induced by chronic A β treatment was achieved at a concentration 10 times lower than that of Epo. In conclusion, EpoL, a new variant of Epo without hematopoietic activity, is of potential interest for the treatment of diseases related to oxidative stress in the CNS such as Alzheimer disease.

show abstract

“…Thus, oxidative stress is inhibited by neuroEPO. It has been reported in rat primary cortical neurons that, under conditions of excitotoxicity, EPO reduces the concentration of free intracellular calcium [ 40 ]. Excessive accumulation of free cytosolic calcium in neurons, caused by the opening of an excessive number of glutamate receptors in the membrane of the neuron leads to the activation and overstimulation the proteases, lipases, phosphatases, and endonucleases [ 41 , 42 ] followed by the activation of several signalling pathways that cause excessive production of free radicals, mitochondrial damage, and cell membrane disruption, which act synergistically causing apoptotic or necrotic neuron death [ 36 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of neuroEPO Using an In Vitro Model of Stroke

Garzón

Rodriguez²,

Cesar

et al. 2018

Behavioral Sciences

View full text Add to dashboard Cite

Erythropoietin (EPO) is a glycoprotein initially identified as a hormone synthesized and secreted by the kidney that regulates erythropoiesis. EPO, and a group of its derivatives, are being evaluated as possible neuroprotective agents in cerebral ischemia. The objective of this study, using an in vitro model, was to determine how neuroEPO—which is a variant of EPO with a low sialic acid content—protects neurons from the toxic action of glutamate. Primary neuronal cultures were obtained from the forebrains of Wistar rat embryos after 17 days of gestation. Excitotoxicity was induced after nine days of in vitro culture by treatment with a medium containing 100 µM glutamate for 15 min. After this time, a new medium containing 100 ng of neuroEPO/mL was added. Morphological cell change was assessed by phase-contrast microscopy. Oxidative stress was analysed by measuring antioxidant and oxidant activity. After 24 h, the treatment with 100 ng of neuroEPO/mL showed a significant (p < 0.01) decrease in mortality, compared to cells treated with glutamate alone. neuroEPO treatment decreased mortality and tended to reproduce the morphological characteristics of the control. The oxidative stress induced by glutamate is reduced after neuroEPO treatment. These results confirm that neuroEPO has a protective effect against neuronal damage induced by excitotoxicity, improving antioxidant activity in the neuron, and protecting it from oxidative stress.

show abstract

Effects of erythropoietin on intracellular calcium concentration of rat primary cortical neurons

Cited by 10 publications

References 40 publications

Erythropoietin alleviates hepatic insulin resistance via PPARγ-dependent AKT activation

Erythropoietin alleviates hepatic insulin resistance via PPARγ-dependent AKT activation

Neuroprotective effects of EpoL against oxidative stress induced by soluble oligomers of Aβ peptide

Neuroprotective Effects of neuroEPO Using an In Vitro Model of Stroke

Contact Info

Product

Resources

About