Abstract

Research Article

Blockage of asymmetric arginine dimethylation of NF-κB and specific knockdown of PRMT4 suppressed lipopolysaccharide/interferon-γ-induced nitric oxide production in glomerular mesangial cells

Kuen-Daw Tsai#, Tsung-Liang Ma#, Wen-Xi Lee, Li-Syuan Wu, Wei Chen, Mei-Huan Li, Bo-Yu Chen, Chia-Ching Lin, Jia-Ching Shieh, Yi-Ju Lee and Ting-Hui Lin*

Published: 17 November, 2021 | Volume 5 - Issue 3 | Pages: 095-106

Prolonged inflammation reactions lead to chronic diseases. Overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated in inflammatory disorders. Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups to their substrates in cellular methylation reactions. PRMTs are emerging as targets for drug discovery because PRMTs are implicated in normal physiology and human diseases. Adenosine dialdehyde (AdOx), a broad-spectrum methyltransferase inhibitor, inhibited lipopolysaccharide and interferon-γ (LPS/IFNγ)-stimulated NO production and iNOS mRNA and protein expression in MES-13 cells. AdOx blocked nuclear factor- κB (NF-κB) nuclear translocation but showed no effect on signal transducer and activator of transcription-1α (STAT-1α) signaling pathway in MES-13 cells. Asymmetrical dimethylation of NF-κB identified by immunoprecipation with ASYM24 antibody was blocked by AMI-1, a specific arginine methyltransferase inhibitor. Moreover, AMI-1 and specific knockdown of protein arginine methyltransferase 4 (PRMT4) with small interfering RNA (siRNA) showed an inhibitory effect on LPS/IFN-γ-stimulated NO and iNOS protein expression in MES-13 cells. Our data suggest asymmetric arginine dimethylation of NF-κB may be implicated in inflammatory disorders though controlling the synthesis of NO, a key mediator in immune activation. The exploration of specific PRMTs, such as PRMT4, involved in iNOS-derived NO synthesis might provide therapeutic applications in treatment of chronic inflammatory diseases.

Read Full Article HTML DOI: 10.29328/journal.jcn.1001082 Cite this Article Read Full Article PDF

Keywords:

Nitric oxide; Inducible nitric oxide synthase; NFκB; adenosine dialdehyde; AMI-1, PRMT4

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