molecular basis for the action of au(i) drugs in rheumatoid arthritis
TRANSCRIPT
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