Protein Information

ID 2448
Name 3 hydroxy 3 methylglutaryl coenzyme A reductase
Synonyms 3 Hydroxy 3 methylglutaryl CoA reductase; 3 Hydroxy 3 methylglutaryl Coenzyme A reductase; Beta hydroxy beta methyl glutaryl CoA reductase; HMG CoA reductase; HMG Coenzyme A reductase; HMGCR; 3 Hydroxy 3 methylglutaryl Coenzyme A reductases; Beta hydroxy beta methyl glutaryl CoA reductases…

Compound Information

ID 1388
Name sodium fluoride
CAS sodium fluoride (NaF)

Reference

PubMed Abstract RScore(About this table)
10946302 Sadeghi MM, Collinge M, Pardi R, Bender JR: Simvastatin modulates cytokine-mediated endothelial cell adhesion molecule induction: involvement of an inhibitory G protein. J Immunol. 2000 Sep 1;165(5):2712-8.
Endothelial cell adhesion molecules (CAMs) E-selectin, ICAM-1, and VCAM-1 play variably important roles in immune-mediated processes. They are induced by the proinflammatory cytokines IL-1 and TNF-alpha, and NF-kappaB is required for the regulated expression of all three genes. Regulators of this pathway could potentially be potent immune modulators. We studied the effect of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, simvastatin, on cytokine-induced expression of CAMs in HUVEC. Unexpectedly, pretreatment with simvastatin potentiated the induction of all three endothelial CAMs by IL-1 and TNF, but not LPS or PMA, as detected by flow cytometry. Northern blot analysis demonstrated an increase in steady state IL-1-induced E-selectin mRNA levels in cells pretreated with simvastatin. This was associated with an increase in nuclear translocation of NF-kappaB, as detected by EMSA. The effect of simvastatin was reversed by mevalonate and geranylgeranyl pyrophosphate but not squalene, indicating that an inhibitory prenylated protein is involved in endothelial responses to proinflammatory cytokines. Pertussis toxin mimicked the effect of simvastatin, and the G protein activator NaF inhibited the cytokine-induced expression of endothelial CAMs, indicating that a Gialpha protein is involved. These results demonstrate that cytokine-mediated activation of the endothelium, and specifically CAM induction, can be modulated by a heterotrimeric G protein-coupled pathway. This may represent a "basal tone" of endothelial inactivation, which can either be disinhibited or amplified, depending on the stimulus.
1(0,0,0,1)