Rthritis: a role for spinal tumor necrosis factor alpha in the course of induction and upkeep of peripheral inflammation. Arthritis Rheum 2010;62:1308?8. CB2 Storage & Stability Coulthard LG, Costello J, Robinson B, et al. Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced arthritis. Arthritis Res Ther 2011;13:R42. Kraus VB, Birmingham J, Stabler Tv, et al. Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254). Osteoarthritis Cartilage 2012;20:271?. Cohen SB, Proudman S, Kivitz AJ, et al. A randomized, double-blind study of AMG 108 (a completely human monoclonal antibody to IL-1R1) in sufferers with osteoarthritis in the knee. Arthritis Res Ther 2011;13:R125. Lin TH, Yang RS, Tang CH, et al. Regulation in the maturation of osteoblasts and osteoclastogenesis by glutamate. Eur J Pharmacol 2008;589:37?4. Szczesniak AM, Gilbert RW, Mukhida M, et al. Mechanical loading modulates glutamate receptor subunit expression in bone. Bone 2005;37:63?3. Wang L, Hinoi E, Takemori A, et al. Release of endogenous glutamate by AMPA receptors expressed in cultured rat costal chondrocytes. Biol Pharm Bull 2005;28:990?. Roth A, Mollenhauer J, Wagner A, et al. Intra-articular injections of high-molecular-weight hyaluronic acid have biphasic effects on joint inflammation and destruction in rat antigen-induced arthritis. Arthritis Res Ther 2005;7:R677?6. Nissler K, Pohlers D, Huckel M, et al. Anti-CD4 monoclonal antibody therapy in acute and early chronic antigen induced arthritis: influence on macrophage activation. Ann Rheum Dis 2004;63:1470?. Pedersen HE. The ossicles in the semilunar cartilages of rodents. Anat Rec 1949;105:1?.27 28
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 289, NO. 34, pp. 23343?3352, August 22, 2014 ?2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.Functional Effects of a Pathogenic Mutation in Cereblon (CRBN) around the Regulation of Protein Synthesis by means of the Na+/K+ ATPase Compound AMPK-mTOR CascadeReceived for publication, October 1, 2013, and in revised kind, June 29, 2014 Published, JBC Papers in Press, July 3, 2014, DOI ten.1074/jbc.M113.Kwang Min Lee1, Seung-Joo Yang, Ja-Hyun Choi, and Chul-Seung Park2 In the School of Life Sciences, Cell Dynamics Study Center and National Major Investigation Laboratory, Gwangju Institute Science and Technology (GIST), Gwangju, 500-712, The Republic of KoreaBackground: Deficiency or nonsense mutation of CRBN causes memory deficits. Benefits: Truncated CRBN has insufficient affinity for AMPK and cannot modulate the AMPK-mTOR pathway. Conclusion: CRBN modulates protein synthesis by way of the AMPK-mTOR pathway, and might be important for particular forms of memory encoding. Significance: Our findings suggest the initial plausible mechanism for the phenotype resulting from the CRBN mutation. Initially identified as a protein implicated in human mental deficit, cereblon (CRBN) was recently recognized as a adverse regulator of adenosine monophosphate-activated protein kinase (AMPK) in vivo and in vitro. Here, we present outcomes showing that CRBN can effectively regulate new protein synthesis by way of the mammalian target of rapamycin (mTOR) signaling pathway, a downstream target of AMPK. Whereas deficiency of Crbn repressed protein translation by means of activation from the AMPKmTOR cascade in Crbn-knock-out mice, ectopic expression in the wild-type CRBN improved protein.
