PMID- 20113495
OWN - NLM
STAT- MEDLINE
DCOM- 20100813
LR  - 20220331
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 12
IP  - 1
DP  - 2010
TI  - A peptidyl-glucosamine derivative affects IKKalpha kinase activity in human 
      chondrocytes.
PG  - R18
LID - 10.1186/ar2920 [doi]
AB  - INTRODUCTION: Nuclear factor-kappaB (NF-kappaB) transcription factor regulates 
      several cell signaling pathways, such as differentiation and inflammation, which 
      are both altered in osteoarthritis. Inhibitor kappaB kinase (IKK)alpha and 
      IKKbeta are kinases involved in the activation of the NF-kappaB transcription 
      factor. The aim of the present study was to determine the effects of glucosamine 
      (GlcN), which is administered in the treatment of osteoarthritis, and of its 
      2-(N-Acetyl)-L-phenylalanylamido-2-deoxy-beta-D-glucose (NAPA) derivative on IKK 
      kinases and, consequently, on NF-kappaB activation in human chondrocytes. 
      METHODS: The human chondrosarcoma cell line HTB-94 and human primary chondrocytes 
      were stimulated with tumor necrosis factor (TNF)alpha after pre-treatment with 
      GlcN or NAPA. Gene mRNA expression level was evaluated by real-time PCR. 
      Inhibitor kappaB protein (IkappaB)alpha phosphorylation and p65 nuclear 
      re-localization were analyzed by Western blotting; IKKalpha nuclear 
      re-localization was also investigated by immunocytochemistry and Western 
      blotting. IKK kinase activity was studied by in vitro kinase assay. RESULTS: 
      After TNFalpha stimulation, the mRNA expression level of some of the genes under 
      NF-kappaB control, such as interleukin (IL)-6 and IL-8, increased, while 
      treatment with GlcN and NAPA reverted the effect. We investigated the possibility 
      that GlcN and NAPA inhibit IKK kinase activity and found that NAPA inhibits the 
      IKKalpha kinase activity, whereas GlcN does not. Interestingly, both GlcN and 
      NAPA inhibit IKKalpha nuclear re-localization. CONCLUSIONS: Our results 
      demonstrate that glucosamine and its peptidyl derivative can interfere with 
      NF-kappaB signaling pathway by inhibiting IKKalpha activity in human 
      chondrocytes. However, the mechanism of action of the two molecules is not 
      completely overlapping. While NAPA can both specifically inhibit the IKKalpha 
      kinase activity and IKKalpha nuclear re-localization, GlcN only acts on IKKalpha 
      nuclear re-localization.
FAU - Scotto d'Abusco, Anna
AU  - Scotto d'Abusco A
AD  - Department of Biochemical Sciences, Sapienza University of Roma, P,le Aldo Moro, 
      5, 00185 Roma, Italy. anna.scottodabusco@uniroma1.it
FAU - Politi, Laura
AU  - Politi L
FAU - Giordano, Cesare
AU  - Giordano C
FAU - Scandurra, Roberto
AU  - Scandurra R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100129
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - N08U5BOQ1K (Glucosamine)
SB  - IM
MH  - Blotting, Western
MH  - Cell Nucleus/metabolism
MH  - Chondrocytes/*enzymology
MH  - Enzyme Activation/*drug effects/physiology
MH  - Gene Expression Profiling
MH  - Glucosamine/analogs & derivatives/*pharmacology
MH  - Humans
MH  - I-kappa B Kinase/*metabolism
MH  - Immunohistochemistry
MH  - Immunoprecipitation
MH  - Microscopy, Confocal
MH  - NF-kappa B/metabolism
MH  - Protein Transport/drug effects
MH  - RNA, Messenger/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2875647
EDAT- 2010/02/02 06:00
MHDA- 2010/08/14 06:00
PMCR- 2010/01/29
CRDT- 2010/02/02 06:00
PHST- 2009/07/20 00:00 [received]
PHST- 2009/12/02 00:00 [revised]
PHST- 2010/01/29 00:00 [accepted]
PHST- 2010/02/02 06:00 [entrez]
PHST- 2010/02/02 06:00 [pubmed]
PHST- 2010/08/14 06:00 [medline]
PHST- 2010/01/29 00:00 [pmc-release]
AID - ar2920 [pii]
AID - 10.1186/ar2920 [doi]
PST - ppublish
SO  - Arthritis Res Ther. 2010;12(1):R18. doi: 10.1186/ar2920. Epub 2010 Jan 29.