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

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.

• Authors: Shen Zhou, Yuan Li, Jing Gao, Yanyan Wang, Xinping Ma, Hui Ding, Xiuling Li, Suofeng Sun
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 2 Pg. 2851-2865 (02 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 35037840 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Phosphoproteins
• Proteome
• Quinolizines
• Protein Kinase C
• Mitogen-Activated Protein Kinases
• Matrines

Topics

• Alkaloids (pharmacology, therapeutic use)
• Hep G2 Cells
• Hepatitis B (drug therapy, metabolism)
• Hepatitis B virus (drug effects, physiology)
• Humans
• MAP Kinase Signaling System (drug effects)
• Mitogen-Activated Protein Kinases (drug effects, metabolism)
• Phosphoproteins (drug effects, metabolism)
• Phosphorylation (drug effects)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Proteome (drug effects, metabolism)
• Quinolizines (pharmacology, therapeutic use)
• Signal Transduction (drug effects)
• Virus Replication (drug effects)
• Matrines