Knockdown of Protein Kinase CK2 Blocked Gene Expression Mediated by Brain‑Derived Neurotrophic Factor-Induced Serum Response Element

Shu-Ping Yang ； Chi‑Yi Lo ； Hui-Min Tseng ； Chih-Chang Chao

《The Chinese Journal of Physiology》 62卷2期 (2019/04) Pp. 63-69

https://doi.org/10.4103/CJP.CJP_1_19

摘要

One of the principal signaling pathway outcomes from brain-derived neurotrophic factor (BDNF) is the activation of antiapoptotic pathways. In addition to the role of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3 kinase, BDNF activates protein kinase CK2 to mediate its neuroprotective effect. The inhibition of CK2 activity has been shown to induce apoptosis. Although serum response element (SRE)-mediated transcription has been reported to be activated by BDNF and that the phosphorylation of serum response factor (SRF) by CK2 has been shown to enhance its DNA binding activity, the biological relevance of these interactions remains largely unclear. In the present study, we found that SRE-mediated transcription, CK2 activity, and SRF phosphorylation increased in PC12 cells under BDNF treatment. The transfection of CK2α siRNA blocked the enhancing effect of BDNF on SRE-mediated transcription, SRF phosphorylation, and Mcl-1 gene expression. Moreover, the blockade of CK2 diminished the antiapoptotic effects of BDNF on SRE-mediated transcription, Mcl-1 gene expression, and cell viability under rotenone-induced cytotoxicity. Our data may assist in the development of therapeutic strategies for inhibiting apoptosis during neurodegeneration.

關鍵字

Antiapoptosis ； brain-derived neurotrophic factor ； Mcl-1 ； protein kinase CK2 ； serum response element-mediated transcription

參考文獻

Zhao H, Alam A, San CY, Eguchi S, Chen Q, Lian Q, et al. Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments. Brain Res 2017;1665:1-21.

Kowiański P, Lietzau G, Czuba E, Waśkow M, Steliga A, Moryś J. BDNF: A Key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol 2018;38:579-93.

Han BH, Holtzman DM. BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK pathway. J Neurosci 2000;20:5775-81.

Xia Y, Wang CZ, Liu J, Anastasio NC, Johnson KM. Brain-derived neurotrophic factor prevents phencyclidine-induced apoptosis in developing brain by parallel activation of both the ERK and PI-3K/Akt pathways. Neuropharmacology 2010;58:330-6.

Chao CC, Ma YL, Lee EH. Brain-derived neurotrophic factor enhances Bcl-xL expression through protein kinase casein kinase 2-activated and nuclear factor kappa B-mediated pathway in rat hippocampus. Brain Pathol 2011;21:150-62.