Calcitonin gene-related peptide enhances CREB phosphorylation and attenuates tau protein phosphorylation in rat brain during focal cerebral ischemia/reperfusion

Zhang, Zhenghong; Xiu-bin, Fang; Xi, Gao; Li, Wen-Chun; Ling, Hai-Yan; Qü, Ping

doi:10.1016/j.biopha.2009.06.009

Cited by 33 publications

(26 citation statements)

References 25 publications

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“…Cerebral ischemia triggers CREB phosphorylation and CRE-mediated gene expression in neurons, such as the antiapoptotic protein Bcl-2, and contributes to survival of neurons and functional recovery in ischemic stroke [45]. In line with it, we found that P-CREB level significantly decreased in the infarct core and peri-infarct region of mouse brain after 6 h MCAO, which may be due to the increase of necrotic or apoptotic neurons in these regions [25]. Interestingly, the decrease of P-CREB level was significantly inhibited in peri-infarct region of 6 h MCAO mice following 25 mg/kg ketamine or 50, 100 mg/kg propofol treatment, which occurred in NeuN positive cells and is consistent with previous reports that in MCAO model, surviving cells showed CRE-mediated gene transcription mainly in the peripheral area surrounding the ischemic core and more than half of the cells were neurons [21,46].…”

Section: Discussionsupporting

confidence: 75%

“…In the brain, the CREB and CRE-mediated genes are involved in neuronal development, regeneration and synaptic plasticity, as well as in neuron survival in response to various ischemic stresses such as hypoxic, oxidative, inflammatory and glutamate excitotoxic stress. Cerebral ischemia triggers the robust phosphorylation of CREB at Ser133 (P-CREB) by various kinases, and then regulates the various gene expressions such as immediate early gene [21,22], neurotrophins [23,24] and anti-apoptotic related protein [25,26], which participate in the protective mechanism of cerebral ischemic injury. The aim of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against 6 h MCAO-induced cerebral ischemic injuries and the involvement of P-CREB.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice

Luo-wa

Han

et al. 2011

Neurochem Res

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Propofol and ketamine may provide certain degree of neuroprotection, but the underlying mechanism remains unclear to date. The cAMP response element-binding protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB) constituted a convergence point involved in neuroprotection. The purpose of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)-induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c mice that underwent 6 h MCAO were randomly divided into eight groups: Sham-operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50, 100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine could significantly reduce the infarct volume, edema ratio and neurological deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in peri-infarct region when compared with that of MCAO + saline group (n = 6 per group). In addition, the results of double-labeled immunofluorescent staining showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri-infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice (n = 4 per group). These results suggested that inhibition of neuron-specific P-CREB dephosphorylation in the peri-infarct region is involved in high dose propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice

Luo-wa

Han

et al. 2011

Neurochem Res

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“…33), which subsequently activates Sp7 transcription factor (SP7, also known as Osterix) and runt-related transcription factor 2 (RUNX2), two other transcription factors that are known to be crucial for osteogenesis 34,35 . We therefore examined these transcription factors in CGRP-treated PDSCs.…”

Section: Resultsmentioning

confidence: 99%

Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats

Zhang

Ruan

et al. 2016

Nat Med

782

550

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Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL-and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.

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“…CGRP can upregulate CREB and its phosphorylation on ser-133 in the rat brain with ischemic neurons 27) . Our data showed that the protein levels of total CREB and pCREB in the nuclei of Huh7 cells cultured with 10 −10 M CGRP were significantly higher than those in control cells, consistent with previous reports.…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Gene-related Peptide Inhibits Tumor Cell Proliferation of Hepatocellular Carcinoma Cells Through the Ras/MEK/ERK Pathway

Hara

Takeba

Watanabe

et al. 2015

J St. Marianna Univ

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Calcitonin gene-related peptide (CGRP) is widely distributed in the central and peripheral nervous systems and regulates physiological functions. Several neuropeptides are involved in the development and progression of hepatocellular carcinoma (HCC), although the role of CGRP in HCC pathogenesis is unclear. This study attempted to clarify the effects of CGRP on tumor progression in HCC cells. CGRP and its receptors, calcitonin receptor-like receptor and receptor activity-modifying protein-1, were expressed in HCC tissues and HCC cell lines. When Huh7 cells were cultured with CGRP 10 M for 24 h, cell proliferation was significantly inhibited. In addition, the total and phosphorylated protein levels of Ras and mitogen-activated protein kinase (MAPK) family proteins, MAP kinase (MEK) 1/2 and extracellular signal-regulated kinase (ERK) 1/2, were also inhibited by CGRP 10 −10 M incubation. CGRP significantly increased the protein levels of cAMP response element binding protein (CREB) and its phosphorylated form in the nuclei of Huh 7 cells. Furthermore, pretreatment of CGRP receptor antagonist CGRP 8-37 abolished the increases in CREB and pCREB protein levels in the nuclei of Huh7 cells. In addition, pretreatment of CGRP 8-37 and cAMP inhibitor Rp-cAMP tended to reverse the ERK inhibition in Huh 7 cells cultured with CGRP. These results suggest that CGRP inhibits HCC cell proliferation via CREB activation and Ras/MEK/ERK pathway. CGRP may play an important role in the amelioration of cancer progression.

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Calcitonin gene-related peptide enhances CREB phosphorylation and attenuates tau protein phosphorylation in rat brain during focal cerebral ischemia/reperfusion

Cited by 33 publications

References 25 publications

Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice

Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice

Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats

Calcitonin Gene-related Peptide Inhibits Tumor Cell Proliferation of Hepatocellular Carcinoma Cells Through the Ras/MEK/ERK Pathway

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