English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), are known to activate sphingomyelinase (SMase) and nuclear factor-κB (NF-κB) in certain cell types, which also stimulate inducible nitric oxide synthase (iNOS) gene in vascular smooth muscle cells (VSMCs). However, it remains unknown whether the SMase pathway is involved in iNOS gene expression in VSMCs. Therefore, the present study was designed to examine whether SMase induces iNOS gene expression via the NF-κB activation pathway similar to that of IL-1β and TNFα in cultured rat VSMCs. Neutral SMase, although less potently than IL-1β and TNFα, stimulated nitrite/nitrate (NOx) production, and iNOS messenger RNA and protein expression, as assessed by Northern and Western blot analyses, respectively. Neutral SMase, IL-1β, and TNFα activated NF-κB, as revealed by electrophoretic mobility shift assay, and its nuclear translocation, as demonstrated by immunocytochemical study. Neutral SMase potentiated NOx production, iNOS expression, and NF-κB activation stimulated by TNFα, but not by IL-1β. Aldehyde peptide proteasome inhibitors completely blocked NOx production, iNOS expression, NF-κB activation, and its nuclear translocation induced by cytokines and neutral SMase. IL-1β and TNFα, but not neutral SMase, caused a transient decrease in IκB-α protein levels, whereas IκB-β protein expression was not affected by either agent. Proteasome inhibitors prevented cytokine-mediated IκB-α degradation. Several cell-permeable ceramide analogs (C2, C6, and C8), hydrolysis products of sphingomyelin, activated NF-κB less potently than neutral SMase, but had no effect on NOx production. These results demonstrate an essential role of NF-κB activation in mediation of neutral SMase-induced iNOS expression, but distinct from the proteasome-mediated IκB-α degradation by cytokines, suggesting the possible involvement of an additional signaling pathway(s).

endocrinology

Role of Nuclear Factor-κB Activation in Cytokine- and Sphingomyelinase-Stimulated Inducible Nitric Oxide Synthase Gene Expression in Vascular Smooth Muscle Cells**This work was supported in part by grants-in-aid from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare of Japan.