Background: Laminar flow protects from atherosclerosis in endothelium. Results: Laminar flow induces Nrf2 activation dependent on ERK5 activation, leading to up-regulation of downstream genes of Nrf2. Conclusion: ERK5 requires Nrf2 activation to exert cytoprotective effect on HUVEC. ERK5 inhibitor BIX02189 regulates Nrf2 activation in vivo. Significance: Identifying ERK5 as a molecular target for regulating flow-mediating Nrf2-dependent gene expression may have significant therapeutic potential for treating atherosclerosis.
In this study, a 40% ethanol extract of Chinese yam flour (Dioscoreae rhizoma), containing 177 +/- 58 microg/mL of dioscin, was tested in order to evaluate its pharmacological effects on the gastrointestinal tracts of Sprague-Dawley rats. Via the ingestion of the Chinese yam extract, the secretion of gastric acid was suppressed in the rats, and gastrointestinal motility increased by as much as 10%. The fecal quantity of rats fed on the Chinese yam extract also increased, by more than 40% as compared with that of the controls. The Chinese yam extract was found not to affect the growth of normal intestinal bacteria. However, a great deal of lactose-fermenting bacteria was observed in the fecal samples of rats fed for 6 weeks on 2% Chinese yam extract. This finding would appear to suggest that Chinese yam extract not only induces an improvement in digestive capability, but also affects the conversion of some intestinal flora to helpful bacteria. Our serochemical analyses indicated that serum glucose, neutral lipid, and total cholesterol levels were reduced to some degree by long-term feeding on Chinese yam extract. This finding bolsters the notion that Chinese yam extract may prove helpful as a digestion-aiding agent for patients suffering from hyperglycemia or hyperlipidemia.
MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-alpha stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-alpha stimulation. To investigate the signaling pathway underlined in TNF-alpha induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-alpha treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-alpha. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-alpha induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-alpha. Taken together, we found that TNF-alpha stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.
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