1. Academic Validation
  2. Novel protein kinase C phosphorylated kinase inhibitor-matrine suppresses replication of hepatitis B virus via modulating the mitogen-activated protein kinase signal

Novel protein kinase C phosphorylated kinase inhibitor-matrine suppresses replication of hepatitis B virus via modulating the mitogen-activated protein kinase signal

  • Bioengineered. 2022 Feb;13(2):2851-2865. doi: 10.1080/21655979.2021.2024957.
Shen Zhou 1 Yuan Li 2 Jing Gao 1 Yanyan Wang 1 Xinping Ma 1 Hui Ding 1 Xiuling Li 1 Suofeng Sun 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • 2 Department of Traditional Chinese Medicine, The Third Affiliated Hospital Affiliated of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China.
Abstract

HBV (hepatitis B virus) Infection still threatens human health. Therefore, it is essential to find new effective anti-HBV compounds. Here, we identified matrine as a novel inhibitor of PKC (protein kinase C) phosphorylated kinase by screening a natural compound library. After HepG2.215 cells were treated with matrine, we carried out a phosphorylated proteomics sequence study and analyzed the prediction of related kinase expression level. In the case of HBV Infection, it was found that PKC kinase mediates the activation of mitogen-activated protein kinase (MAPK) signaling pathway known as son of sevenless (SOS) activation. It was also found that PKC kinase inhibits the expression of C-X-C Motif Chemokine Ligand 8 (CXCL8) by inhibiting the activity of activating transcription factor 2/ cAMP response element binding protein (ATF2/CREB), and this effect is independent of its activated MAPK signaling pathway. Finally, Western blot was used to detect the expression of MAPK, ATF2, CREB3 phosphorylation and nonphosphorylation in matrine-treated cells and PKC-treated cells. PKC phosphorylated kinase inhibitor-matrine suppresses the replication of HBV via modulating the MAPK/ATF2 signal. Matrine is a good clinical drug to enhance the autoimmunity in the Adjuvant treatment of chronic HBV Infection.

Keywords

HBV; MAPK signaling pathway; Matrine; PKC; phosphoproteome analysis.

Figures
Products