Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

Xie, Keqiang; Zhang, Limin; Cao, Yan; Zhu, Jun; Feng, Linyin

doi:10.1038/aps.2009.80

Cited by 21 publications

(21 citation statements)

References 33 publications

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“…This Akt and ERK1/2 signaling protected neurons and cardiac cells against injury from ischemia and reperfusion in vitro [18,19] .…”

Section: Egfr Is Involved In Akt and Erk1/2 Phosphorylation In Responmentioning

confidence: 87%

“…It has been shown that A 1 R transactivation of EGFR exerts protective effects against ischemia and reperfusion [18,19] . PF acted at the surface of HEK293/A 1 R cells to promote an interaction between A 1 R and EGFR, which increased signal transduction from the two receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Cortical neurons were cultured from Sprague-Dawley rats at embryonic day 18 (E18) using a modified method that has been previously described [18] . Fetal brains were removed under sterile conditions.…”

Section: Primary Culture Of Cortical Neuronsmentioning

confidence: 99%

“…In each experiment, cultures exposed to OGD/R were compared with normoxic controls, which were maintained under standard incubation conditions. [18,21] . Cells were cultured in DMEM supplemented with 10% FBS and 500 μg/mL G418, and cultured at 37 °C with 5% CO 2 humidified air.…”

Section: Primary Culture Of Cortical Neuronsmentioning

confidence: 99%

“…Several phosphorylation sites in the C-terminal domain of EGFR, when activated, further stimulate the activation of downstream signaling pathways, including MAPK, Akt, and JNK [17] . The selective A 1 R agonist cyclopentyladenosine (CPA) promotes neuronal survival after an OGD/R injury, most likely through PI3K/Akt signaling induced by A 1 R-mediated transactivation of EGFR [18] . Consistent with its role in neuronal protection, it has also been found that A 1 Rmediated transactivation of EGFR protects cardiac cells against ischemia and reperfusion [19] .…”

Section: Introductionmentioning

confidence: 99%

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Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor

Zhong

Song

et al. 2015

Acta Pharmacol Sin

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Aim: Paeoniflorin from Chinese herb Paeoniae Radix has been shown to ameliorate middle cerebral artery occlusion-induced ischemia in rats. The aim of this study was to investigate the mechanisms underlying the neuroprotective action of PF in cultured rat cortical neurons. Methods: Primary cultured cortical neurons of rats were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) insult. Cell survival was determined using MTT assay. HEK293 cells stably transfected with A 1 R (HEK293/A 1 R) were used for detailed analysis. Phosphorylation of the signaling proteins was evaluated by Western blot or immunoprecipitation. Receptor interactions were identified using co-immunoprecipitation and immunofluorescence staining. Results: Paeoniflorin (10 nmol/L to 1 μmol/L) increased the survival of neurons subjected to OGD/R. Furthermore, paeoniflorin increased the phosphorylation of Akt and ERK1/2 in these neurons. These effects were blocked by PI3K inhibitor wortmannin or MEK inhibitor U0126. Paeoniflorin also increased the phosphorylation of Akt and ERK1/2 in HEK293/A 1 R cells. Both A 1 R antagonist DPCPX and EGFR inhibitor AG1478 not only blocked paeoniflorin-induced phosphorylation of ERK1/2 and Akt in HEK293/A 1 R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. In addition, paeoniflorin increased the phosphorylation of Src kinase and activation of MMP-2 in HEK293/A 1 R cells. Both Src inhibitor PP2 and MMP-2/MMP-9 inhibitor BiPs not only blocked paeoniflorininduced phosphorylation of ERK1/2 (and Akt) in HEK293/A 1 R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. Conclusion: Paeoniflorin promotes the survival of cultured cortical neurons by increasing Akt and ERK1/2 phosphorylation via A 1 Rmediated transactivation of EGFR.

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“…This Akt and ERK1/2 signaling protected neurons and cardiac cells against injury from ischemia and reperfusion in vitro [18,19] .…”

Section: Egfr Is Involved In Akt and Erk1/2 Phosphorylation In Responmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Primary Culture Of Cortical Neuronsmentioning

confidence: 99%

Section: Primary Culture Of Cortical Neuronsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor

Zhong

Song

et al. 2015

Acta Pharmacol Sin

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Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Zhi

Wang

et al. 2012

IUBMB Life

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SummaryCD73, an ecto-enzyme overexpressed in breast-cancer cells, catalyzes the dephosphorylation of adenosine monophosphates into adenosine. Anti-CD73 slows breast cancer growth and its spread both in vivo and in vitro. In this study, we investigated the relation of CD73 to epidermal growth factor receptor (EGFR) expression using tissue array and breast cancer cell lines. We found that CD73 expression correlated positively to EGFR expression in vivo (n 5 80, r 5 0.425, P \ 0.01) and in vitro. EGFR expression can be decreased by suppressing CD73 with an inhibitor or small shRNA, and this effect was reversed by adenosine and NECA (adenosine A2 receptor agonist), which suggested that adenosine is involved in EGFR expression regulated by CD73 (P \ 0.01). We also showed that CD73 regulates EGFR phosphorylation by Src (P \ 0.01). By transcription factor (TF) assay, CD73 was found to regulate some associated TFs activity such as PPARc, which mediates EGFR expression, although whether PPARc mediates the effect of CD73 on EGFR expression needs further study. The KaplanMeier recurrence-free survival curves for CD73 were also plotted in www.kmplot.com. The curves show that CD73 expression separates the cases into significantly different prognostic groups among the estrogen receptor-negative cancers (P \ 0.01). Our results suggest that CD73 may be a potential prognostic biomarker associated with coexpression of EGFR in human breast cancer.2012 IUBMB IUBMB Life, 64(11): 911-920, 2012

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The Role of Receptor Transactivation in the Cardioprotective Effects of Preconditioning and Postconditioning

Maslov

Headrick

Mechoulam

et al. 2013

Neurosci Behav Physi

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Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

Cited by 21 publications

References 33 publications

Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor

Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

The Role of Receptor Transactivation in the Cardioprotective Effects of Preconditioning and Postconditioning

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