Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Apr 2004
The tea flavonoid epigallocatechin-3-gallate reduces cytokine-induced VCAM-1 expression and monocyte adhesion to endothelial cells.
Attachment of leukocytes to the vascular endothelium and the subsequent migration of cells into the vessel wall are early events in atherogenesis. This process requires the expression of endothelial adhesion molecules. Since tea catechins are reputed to promote antiatherogenic activities, we investigated the effects of various tea catechins-i.e., epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin-3-gallate (EGCG)-on cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) in HUVECs by ELISA. ⋯ Inhibition of cytokine-induced VCAM-1 expression was manifested already on the transcriptional level. Furthermore, EGCG reduced the TNF-alpha-induced adhesion of THP-1 cells to HUVECs. EGCG did not influence TNF-alpha-stimulated NF-kappaB activation.
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Biochem. Biophys. Res. Commun. · Apr 2004
Transcription factor Sp1 mediates p38MAPK-dependent activation of the p21WAF1 gene promoter in vascular smooth muscle cells by pyrrolidine dithiocarbamate.
Previously, we demonstrated that pyrrolidine dithiocarbamate (PDTC) induced G1 cell cycle arrest in vascular smooth muscle cells (VSMC) through inducing p21WAF1 expression. It has recently been reported that the transcription factors involved in p21WAF1 activation by certain signaling factors may vary in different cell types. However, little is known concerning the molecular mechanisms by which PDTC induces p21WAF1 gene expression in VSMC. ⋯ Treatment with SB203580, an inhibitor of the p38MAPK, significantly down-regulated transactivation of PDTC-induced Sp1. Finally, the transient expression of VSMC with dominant negative p38MAPK plasmid suppressed PDTC-stimulated Sp1 activity. In conclusion, we report the novel finding that transcription factor Sp1 that is involved in the p38MAPK-mediated control of p21WAF1 regulation on VSMC in response to PDTC has now been identified.
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Biochem. Biophys. Res. Commun. · Apr 2004
Antioxidative treatment reverses imbalances of nitric oxide synthase isoform expression and attenuates tissue-cGMP activation in diabetic rats.
Oxidative stress and impaired bioactivity of vascular nitric oxide (NO) play an important role in the pathogenesis of macro- as well as microangiopathic complications in diabetes mellitus. To determine the cause of this impaired bioactivity, we tested the effect of long-term hyperglycemia and antioxidative treatment on tissue-specific endothelial (e)NOS- and inducible (i)NOS-expression and the main target of NO action, cGMP, in diabetic rats. After 4 weeks of hyperglycemia, eNOS-mRNA expression was significantly down-regulated in all tissues tested. ⋯ In addition, our data suggest that the cause of impaired endothelial vasodilatation in experimental diabetes is not degradation or inactivation of NO. On the contrary, these results support the concept of decreased reactivity of the vascular smooth muscle to NO or increased NO activity as a possible vascular damaging agent, e.g., by inducing apoptosis in vascular cells. Furthermore, our data show that antioxidative treatment is capable of reversing changes in the NO-cGMP system and may therefore be an important therapeutic option for preventing vascular damage in diabetes mellitus.