Multiple subcellular localizations and functions of protein kinase Cδ in liver cancer

Yamada, Kohji; Yoshida, Kiyotsugu

doi:10.3748/wjg.v28.i2.188

Cited by 4 publications

(1 citation statement)

References 85 publications

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“…In addition, CaSR has been demonstrated to activate Ca 2+ -dependent protein kinase C (PKC) and induce the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) [18]. PKC, a family of serine/threonine protein kinases, participates in many cellular responses such as cell proliferation [19]. To date, conventional PKC isoforms have been identi ed require Ca 2+ in ux for their activation [20].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Calcium-Sensing Receptor Alleviates Chronic Intermittent Hypoxia-Induced Cognitive Dysfunction via CaSR-PKC-ERK1/2 Pathway

et al. 2023

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Obstructive sleep apnea hypopnea syndrome (OSAHS) is typically characterized by chronic intermittent hypoxia (CIH), associated with cognitive dysfunction in children. Calcium-sensing receptor (CaSR), a member of G-protein coupled receptors superfamily, has been demonstrated to mediate the apoptosis of hippocampal neurons in various diseases. However, the effect of CaSR on OSAHS remains elusive. In the present study, we investigated the role of CaSR in CIH-induced memory dysfunction and underlying mechanisms on regulation of PKC-ERK1/2 signaling pathway in vivo and in vitro. CIH exposures for 4 weeks in mice, modeling OSAHS, contributed to cognitive dysfunction, manifested as increased working memory errors, reference memory errors and total memory errors. CIH accelerated apoptosis of hippocampal neurons by increased TUNEL positive cells, up-regulated cleaved-Caspase3 and downregulated Bcl-2 in mice, and resulted in the synaptic plasticity de cit via down-regulated synaptophysin (Syn) protein level. To further identify whether CaSR is involved in hippocampal neuronal apoptosis and synaptic plasticity induced by CIH, the mice were intraperitoneally injected with CaSR inhibitor (NPS2143) 30 min before CIH exposure everyday, and the results demonstrated CaSR inhibitor alleviated the apoptosis and synaptic plasticity de cit in the hippocampus of CIH mice, accompanied by decreased p-ERK1/2 and PKC. To clarify the mechanism of apoptosis and synaptic plasticity in CIH hippocampal neurons mediated by CaSR, we established intermittent hypoxia PC12 cell model and found that the activation of CaSR accelerated CIH-induced PC12 apoptosis and synaptic plasticity de cit by upregulated p-ERK1/2 and PKC. Overall, our ndings indicated that CaSR held a critical function on CIHinduced cognitive dysfunction in mice by accelerating hippocampal neuronal apoptosis and reducing synaptic plasticity via augmenting CaSR-PKC-ERK1/2 pathway; otherwise, inhibition of CaSR alleviated CIH-induced cognitive dysfunction.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Calcium-Sensing Receptor Alleviates Chronic Intermittent Hypoxia-Induced Cognitive Dysfunction via CaSR-PKC-ERK1/2 Pathway

et al. 2023

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Microtubule-affinity regulating kinase 4: A potential drug target for cancer therapy

Anwar

Shahwan

Hasan

et al. 2022

Cellular Signalling

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Inhibition of Calcium-sensing Receptor Alleviates Chronic Intermittent Hypoxia-induced Cognitive Dysfunction via CaSR-PKC-ERK1/2 Pathway

Ying

Zhang

Wang

et al. 2022

Preprint

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Obstructive sleep apnea hypopnea syndrome (OSAHS) is typically characterized by chronic intermittent hypoxia (CIH), associated with cognitive dysfunction in children. Calcium-sensing receptor (CaSR), a member of G-protein coupled receptors superfamily, has been demonstrated to mediate the apoptosis of hippocampal neurons in various diseases. However, the effect of CaSR on OSAHS remains elusive. In the present study, we investigated the role of CaSR in CIH-induced memory dysfunction and underlying mechanisms on regulation of PKC-ERK1/2 signaling pathway in vivo and in vitro. CIH exposures for 4 weeks in mice, modeling OSAHS, contributed to cognitive dysfunction, manifested as increased working memory errors, reference memory errors and total memory errors. CIH accelerated apoptosis of hippocampal neurons by increased TUNEL positive cells, up-regulated cleaved-Caspase3 and down-regulated Bcl-2 in mice, and resulted in the synaptic plasticity deficit via down-regulated synaptophysin (Syn) protein level. To further identify whether CaSR is involved in hippocampal neuronal apoptosis and synaptic plasticity induced by CIH, the mice were intraperitoneally injected with CaSR inhibitor (NPS2143) 30 min before CIH exposure everyday, and the results demonstrated CaSR inhibitor alleviated the apoptosis and synaptic plasticity deficit in the hippocampus of CIH mice, accompanied by decreased p-ERK1/2 and PKC. To clarify the mechanism of apoptosis and synaptic plasticity in CIH hippocampal neurons mediated by CaSR, we established intermittent hypoxia PC12 cell model and found that the activation of CaSR accelerated CIH-induced PC12 apoptosis and synaptic plasticity deficit by up-regulated p-ERK1/2 and PKC. Overall, our findings indicated that CaSR held a critical function on CIH-induced cognitive dysfunction in mice by accelerating hippocampal neuronal apoptosis and reducing synaptic plasticity via augmenting CaSR- PKC-ERK1/2 pathway; otherwise, inhibition of CaSR alleviated CIH-induced cognitive dysfunction.

show abstract

Multiple subcellular localizations and functions of protein kinase Cδ in liver cancer

Cited by 4 publications

References 85 publications

Inhibition of Calcium-Sensing Receptor Alleviates Chronic Intermittent Hypoxia-Induced Cognitive Dysfunction via CaSR-PKC-ERK1/2 Pathway

Inhibition of Calcium-Sensing Receptor Alleviates Chronic Intermittent Hypoxia-Induced Cognitive Dysfunction via CaSR-PKC-ERK1/2 Pathway

Microtubule-affinity regulating kinase 4: A potential drug target for cancer therapy

Inhibition of Calcium-sensing Receptor Alleviates Chronic Intermittent Hypoxia-induced Cognitive Dysfunction via CaSR-PKC-ERK1/2 Pathway

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