Inhibition of spermidine/spermine N1-acetyltransferase activity: a new therapeutic concept in rheumatoid arthritis
Results: RASFs showed elevated SSAT-1, AMD, and PMF-1 levels. However, PMF-1 promoter methylation was unchanged. Transfection of siRNA targeting SSAT-1 increased 5-MeC levels within 21 days. Similarly, DA increased 5-MeC levels in RASFs. In addition, DA increased the levels of DNMT-1, decreased the levels of AMD, putrescine, activation markers, and MMP-1, and altered the adhesion of RASFs. DA was more efficient in RASFs with higher levels of SSAT-1. Most interestingly, the combination of DA and SAM reduced the invasiveness of RASFs by 70%.
Conclusion: The use of DA alone or in combination with SAM/L-methionine might introduce a new therapeutic concept in RA. This is the first therapy that would directly target RASFs and thereby inhibit ongoing joint destruction.
Results: RASFs showed elevated SSAT-1, AMD, and PMF-1 levels. However, PMF-1 promoter methylation was unchanged. Transfection of siRNA targeting SSAT-1 increased 5-MeC levels within 21 days. Similarly, DA increased 5-MeC levels in RASFs. In addition, DA increased the levels of DNMT-1, decreased the levels of AMD, putrescine, activation markers, and MMP-1, and altered the adhesion of RASFs. DA was more efficient in RASFs with higher levels of SSAT-1. Most interestingly, the combination of DA and SAM reduced the invasiveness of RASFs by 70%.
Conclusion: The use of DA alone or in combination with SAM/L-methionine might introduce a new therapeutic concept in RA. This is the first therapy that would directly target RASFs and thereby inhibit ongoing joint destruction.
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