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Molecular basis for the action of Au(I)
drugs in rheumatoid arthritis
Rheumatoid arthritis
immune system attacks joints
chronic inflammatory disease
Wikipedia - Joint , Rheumatoid Arthritis
Anti-inflammatory and immunomodulatory effects of gold(I)-containing drugs
J. Biol. Chem., Vol. 276, Issue 36, 34074-34081, September 7, 2001
Collagenase
interleukin- 2 (IL-2)
proteins involved in promoting inflammation
Cytokines
interleukin-2 receptor
genes involved in promoting inflammation
down-regulated
Anti-inflammatory and immunomodulatory effects of gold(I)-containing drugs
J. Biol. Chem., Vol. 276, Issue 36, 34074-34081, September 7, 2001
antioxidative stress proteins
g - glutamylcysteine synthetase
antioxidative stress genes
induce
heme oxygenase
GO
Transcription factors
http://en.wikipedia.org/wiki/Transcription_factor
http://www.ndsu.edu/instruct/mcclean/plsc731/transcript/transcript1.htm
http://www.piercenet.com/Proteomics/browse.cfm?fldID=843944B3-65F9-42A9-BF7A-6F91B4A6FBBB
facilitate or inhibit gene expression
Regulatory Region Gene
Transcription
DNA
c-Jun c-FosRNA
Polymerase II
AP-1 transcription factor
TGACTCA
Gold(I)-drugs inhibit AP-1
Electrophoresis
EMSA
Electrophoretic Mobility Shift Assay
Lane 1 is a negative control, and contains only DNA. Lane 2 contains protein as well as a DNA fragment that, based on its sequence, does not interact. Lane 3 contains protein and a DNA fragment that does react; the resulting complex is larger, heavier, and slower-moving.
Gel Electrophoresis
Gold(I)-drugs inhibit AP-1 binding to DNA
Proc. Natl. Acad. Sci. USA Vol. 92, pp. 4497-4501, May 1995
Effect of Gold(I)-drugs on other transcription factors
Proc. Natl. Acad. Sci. USA Vol. 92, pp. 4497-4501, May 1995
Gold(I) inhibition of transcription in vivo
Regulatory Region Gene for CAT
Transcription
DNA
c-Jun c-FosRNA
Polymerase II
AP-1 transcription factor
TGACTCA
(CAT) chloramphenicol acetyltransferasereporter gene
Interaction of Cys residues on Jun and Fos with Au(I)
Proc. Natl. Acad. Sci. USA Vol. 92, pp. 4497-4501, May 1995
~CH2SH ~CH2OH
AP-1 : DNA interaction
Nature vol. 373, pp.257-261, 1995
AP-1 : DNA interaction
Nature vol. 373, pp.257-261, 1995
AP-1 : DNA interaction
Nature vol. 373, pp.257-261, 1995