Cycloprodigiosin up-regulates inducible nitric oxide synthase gene expression in hepatocytes stimulated by interleukin-1beta

Nitric Oxide : Biology and Chemistry
Shigeru TeshimaTadayoshi Okumura

Abstract

The proinflammatory cytokine interleukin-1beta stimulates inducible nitric oxide synthase (iNOS) gene expression in hepatocytes via activation of a transcription factor, nuclear factor-kappaB (NF-kappaB). Nitric oxide has diverse cytoprotective and toxic effects. Cycloprodigiosin is an anticancer drug that induces apoptosis through NF-kappaB-dependent mechanisms. This study investigated whether cycloprodigiosin influenced NF-kappaB activation and induction of iNOS by interleukin-1beta. Cycloprodigiosin alone had no effect on NO production by primary cultured rat hepatocytes. Simultaneous addition of cycloprodigiosin and interleukin-1beta markedly stimulated the induction of iNOS mRNA and protein compared with addition of interleukin-1beta alone, resulting in overproduction of NO. Cycloprodigiosin had no effect on degradation of the inhibitory subunit of NF-kappaB (IkappaBalpha), but lessened the recovery of IkappaBalpha levels. The electrophoretic mobility shift assay revealed that cycloprodigiosin caused an increase of NF-kappaB activation. Consistent with this observation, cycloprodigiosin promoted the translocation of p65 (a subunit of NF-kappaB) to the nucleus. Furthermore, this drug enhanced expression of the type 1 interl...Continue Reading

References

Oct 1, 1982·Analytical Biochemistry·L C GreenS R Tannenbaum
Dec 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·I BohlingerA Wendel
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D A GellerT R Billiar
Feb 26, 1993·Biochemical and Biophysical Research Communications·Y NunokawaS Tanaka
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·M E de VeraD A Geller
Jun 25, 1996·Biochemical and Biophysical Research Communications·W EberhardtJ Pfeilschifter
Apr 4, 1998·The Journal of Experimental Medicine·C HierholzerD J Tweardy
Feb 15, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·M NishizawaS Ito
Aug 30, 2000·International Journal of Cancer. Journal International Du Cancer·D YamamotoK Hioki
Oct 26, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T InoueT Okumura

❮ Previous
Next ❯

Citations

May 7, 2014·Marine Drugs·Maria Alessandra GammoneNicolantonio D'Orazio
Jan 12, 2011·Digestive Diseases and Sciences·Yoshiro ArakiA-Hon Kwon
Aug 23, 2007·JPEN. Journal of Parenteral and Enteral Nutrition·Kosuke MatsuiTadayoshi Okumura
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xue LiBaolei Jia

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis