Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension.
Hypoxia induces plant stress, particularly in cucumber plants under hydroponic culture. In plants, calcium is involved in stress signal transmission and growth. The ultimate goal of this study was to shed light on the mechanisms underlying the effects of exogenous calcium on the mitochondrial antioxidant system, the activity of respiratory metabolism enzymes, and ion transport in cucumber (Cucumis sativus L. cv. Jinchun No. 2) roots under hypoxic conditions. Our experiments revealed that exogenous calcium reduces the level of reactive oxygen species (ROS) and increases the activity of antioxidant enzymes in mitochondria under hypoxia. Exogenous calcium also enhances the accumulation of enzymes involved in glycolysis and the tricarboxylic acid (TCA) cycle. We utilized fluorescence and ultrastructural cytochemistry methods to observe that exogenous calcium increases the concentrations of Ca2+ and K+ in root cells by increasing the activity of plasma membrane (PM) H+-ATPase and tonoplast H+-ATPase and H+-PPase. Overall, our results suggest that hypoxic stress has an immediate and substantial effect on roots. Exogenous calcium improves metabolism and ion transport in cucumber roots, thereby increasing hypoxia tolerance in cucumber.
A new natural product (N-acetyltryptophan), together with 22 known constituents, including seven alkaloids, six flavonoids, six organic acids, and other compounds, were isolated from Salsola collina Pall. Their structures were elucidated on the basis of chemical reaction and spectral evidence. Among the isolated compounds, N-acetyltryptophan (8) showed moderate inhibition of D-amylase activity, and terrestric acid (9) showed positive antifungal activity.Salsola collina Pall., which is widely distributed in northeastern and southwestern China, has been used as food or folk medicine for the treatment of hypertension, headache, and vertigo in China. Few phytochemical investigations of the plant have been previously reported, and they mainly refer to the isolation of sterols >1@, sugars, sugar esters >2@, flavonoids >3-6@, and alkaloids >7, 8@. Salsoline A, an alkaloid isolated from Salsola collina Pall., showed appreciable antibacterial activity and moderate antiviral activity against influenza virus A and B >9@. To isolate new compounds and to search for biologically active compounds from Salsola collina Pall., we have carried out a phytochemical investigation of it, obtaining 23 compounds, which were pericampylinone-A (1) >10@, salsoline A (2) >7@, moupinamide (3) >11@, 7c-hydroxymoupinamide (4) >12@, 7c-hydroxy-3c-methylmoupinamide (5) >12@, uracil (6) >13@, uridine (7) >14@, N-acetyltryptophan (8) >15, 16@ terrestric acid (9) >17@, anisic acid (10), protocatechuic aldehyde (11), vanillin (12) >18@, corchoionoside C (13) >19@, acetyl ferulic acid (14) >20@, p-hydroxycinnamic acid (15) >8@, salicylic acid (16), isorhamnetin (17) >21], tricin (18) >22@, tricin-7-O-E-Dglucopyranoside (19) >8@, 5,2c-dihydroxy-6,7-methylenedioxyisoflavone (20) >23@, quercetin (21) >24@, rutin (22) >25@ and p-hydroxybenzoic acid (23). Among these compounds, N-acetyltryptophan (8) was a new natural product, and compounds 1-9 and 11-14 were isolated from this plant for the first time. The biologically active results showed that N-acetyltryptophan (8) had moderate D-amylase inhibitory activity (Table 1), and terrestric acid (9) had positive antifungal activity (Table 2). NH O HO HO 1 N O HO HO 2 HN N O O R 6, 7 6: R = H; 7: R = ribose N H 3 CO HO O R 2 R 1 OH H 3 -5 3: R 1 = R 2 = H; 4: R 1 = H, R 2 = OH 5: R 1 = OCH 3 , R 2 = OH
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