title: Curcumin promotes degradation of inducible nitric oxide synthase and suppresses its enzyme activity in RAW 264.7 cells.
abstract: Curcumin, a natural polyphenolic compound, has been reported to possess anti-inflammatory properties. Previous works showed that curcumin decreased lipopolysaccharide (LPS)-induced iNOS up-regulation at transcription level. However, whether curcumin could regulate iNOS at the post-translational level is still unclear. In the present study, we demonstrated that curcumin promoted the degradation of iNOS which is expressed under LPS stimulation in murine macrophage-like RAW 264.7 cells. Mechanically, such degradation of iNOS protein is due to ubiquitination and proteasome-dependency since it was almost completely blocked by N-benzoyloxycarbonyl-Leu-Leu-leucinal (MG132), a specific inhibitor of proteasome. Furthermore, curcumin decreased iNOS tyrosine phosphorylation through inhibiting ERK 1/2 activation and subsequently suppressed iNOS enzyme activity. In conclusion, our research displays a new finding that curcumin can promote the ubiqitination and degradation of iNOS after LPS stimulation.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Peiling
authors.initials: P
authors.lastname: Ben
authors.forename: Junhong
authors.initials: J
authors.lastname: Liu
authors.forename: Changyan
authors.initials: C
authors.lastname: Lu
authors.forename: Yimiao
authors.initials: Y
authors.lastname: Xu
authors.forename: Yinqiang
authors.initials: Y
authors.lastname: Xin
authors.forename: Jin
authors.initials: J
authors.lastname: Fu
authors.forename: Huang
authors.initials: H
authors.lastname: Huang
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gao
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D054875:Ubiquitination
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D003474:Curcumin