Overexpression of RAPGEF3 enhances the therapeutic effect of dezocine in treatment of neuropathic pain

Abstract

Pain is a significant problem worldwide that affects the quality of life of patients. Dezocine is a non-addictive analgesic drug with kappa-opioid antagonist activity and has been successfully used to alleviate of postoperative pain. In addition, dezocine has an analgesic effect similar to that of morphine, alleviating moderate to severe pain. Rap guanine nucleotide exchange factor 3 (RAPGEF3) is a guanine nucleotide exchange factor for GTPases Rap1 and Rap2, which could enhance the activity of Rap1 to promote cell adhesion and axon regeneration, as well as promote neurite extension by interacting with nerve growth factors. Here, we first observed that overexpression of RAPGEF3 increased cell viability, as shown by a CCK-8 assay, and recovered brain function in rats. The expression of inflammation-related factors at the mRNA level was detected using qPCR, and the concentration of these factors in a cultured cell medium and rat serum samples were decreased as shown by ELISA after RAPGEF3 overexpression. Through western blotting, we further found that pro-inflammatory proteins were decreased, and these effects might be mediated by inhibition of the Ras/p-38 MAPK signaling pathway. Taken together, we speculated that RAPGEF3overexpression enhances the therapeutic effect of dezocine on neuropathic pain by inhibiting the inflammatory response through inhibition of the Ras/p-38 MAPK signaling pathway.

RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation

“…In contrast, the amounts of GPCR Prkar1b ( Marbach et al, 2021 ), P2ry12 ( Defaye et al, 2021 ), and Htr2c ( Brasch-Andersen et al, 2011 ) in the TG were dramatically decreased after CFA injection. For the ion channels, we observed that the noticeably elevated expression of Rapgef3 ( Liu et al, 2021 ), Nos1 ( Shnayder et al, 2021 ), TRPM8 ( Weyer and Lehto, 2017 ), and CXCL12 ( Luo et al, 2016 ) in the TG were remarkably increased after CFA injection. On the contrary, the levels of ion channel transcripts for Sgk3 ( Liu et al, 2015 ) was significantly reduced in the TG after CFA injection.…”

A‐to‐I RNA Editing in Klebsiella pneumoniae Regulates Quorum Sensing and Affects Cell Growth and Virulence

“…[7,8] An increasing amount of work has also led to the discovery and identification of RNA editing sites in fungi. [9][10][11] However, RNA editing regulation in bacteria has rarely been reported. Recently, Bar-Yaacov et al provided evidence of RNA editing in Escherichia coli on hokB, which encodes a toxin that confers antibiotic tolerance, that increases as a function of cell density and enhances the toxicity of the protein.…”