We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on the regulation of systolic blood pressure (SBP) and oxidative stress through endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHRs). SHRs randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat was measured before and weekly thereafter. After a total of 8-week treatment, rats were killed for experimental measurements. Parameters that subject to measurements in isolated aorta endothelial cells include: NO concentration, protein expression levels of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also applied to test the inhibition of NO concentration. We found that SBPs were significantly lower in telmisartan therapy group than in placebo treated hypertensive rats and WKYs (p<0.05). The NO concentration was significantly higher in telmisartan-treated group with increased activity of the PI3K/Akt pathway and activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment reduced less NO concentration in SHR rats than the telmisartan co-treated groups. Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK phosphorylation and eNOS expression, which attenuated the blood pressure and oxidative stress in SHRs., L. Xu, Y. Liu., and Obsahuje seznam literatury
B cell-activating factor belonging to the TNF family (BAFF, also called BLyS, TALL-1, zTNF-4, or THANK) is an important survival factor for B lymphocytes. In this study, we injected mouse abdominal cavity with human soluble BAFF (hsBAFF, 0.01, 0.1, 0.5, 2 mg/kg body mass) synthesized in Escherichia coli. On the 8th day after injection, we investigated the effects of hsBAFF on immune functional activities of splenic B lymphocytes, CD4+ and CD8+ T lymphocytes and natural killer (NK) cells in mice. The results showed that B lymphocyte proliferation significantly increased in hsBAFF-treated groups with dosages of 0.1 mg/kg (p<0.05), 0.5 and 2 mg/kg (p<0.01). We observed a dose-dependent increase of CD4+ T lymphocyte percentage and significantly higher values in 0.5 and 2 mg/kg hsBAFF-treated groups (p<0.05 and p<0.001, respectively) compared to control group, but CD8+ T lymphocyte percentage remained unchanged. The ratio of CD4+ to CD8+ T lymphocytes rose with increasing hsBAFF dosage (p<0.05 for 2 mg/kg hsBAFF vs. control). Significantly stronger NK cell activities were found in 0.5 and 2 mg/kg hsBAFF-treated groups (p<0.05). The main finding of this study is that the hsBAFF can enhance immune responses in the body by increasing B lymphocyte and CD4+ T lymphocyte function as well as elevating NK cell activity.
5-aminolevulinic acid (ALA) is an essential precursor for the biosynthesis of tetrapyrrols such as heme and chlorophyll (Chl). Previous studies have focused mainly on promotive effects of exogenous ALA on plant growth, while regulatory mechanisms affecting Chl biosynthesis have been only partially discussed. In the present study, the ameliorative role of exogenous ALA was investigated on Chl and endogenous ALA biosynthesis in six-day-old etiolated oilseed rape (Brassica napus L.) cotyledons during the de-etiolation stage. We showed that exogenously applied ALA of a low dosage enhanced Chl and ALA accumulation in cotyledons, while 600 µM ALA treatment inhibited the accumulation of Chl and ALA severely. However, the gene expression levels of glutamyl-tRNA reductase (HEMA) and glutamate-1-semialdehyde aminotransferase (GSA) were not affected under either low or high ALA concentrations. Furthermore, water deficit induced by polyethylene glycol 6000 (PEG) suppressed the Chl and ALA accumulation in cotyledons, while the inhibition was partially alleviated in the cotyledons pretreated with ALA. The decrease in Chl biosynthesis induced by PEG stress was assumed to be related to downregulation of HEMA and Mg-chelatase ChlH (ChlH), and upregulation of ferrochelatase (FC) genes. Moreover, exogenously applied ALA did not show any effect on the expression of Chl synthesis-related genes under the PEG treatment. These results showed a difference in suppressing ALA synthesis due to the high concentration of ALA and PEG. Exogenously applied ALA did not affect the expression of HEMA and GSA, thus exogenous ALA regulated Chl synthesis not via the regulation of transcriptional level in ALA biosynthesis. However, the inhibition in Chl and endogenous ALA accumulation by the PEG treatment may be attributed to downregulation of HEMA and ChlH, and upregulation of FC., D. Liu, D. D. Kong, X. K. Fu, B. Ali, L. Xu, W. J. Zhou., and Seznam literatury
The present study investigated the effects of nesfatin-1 on gastric distension (GD)-responsive neurons via an interaction with corticotropin-releasing factor (CRF) receptor signaling in the ventromedial hypothalamic nucleus (VMH), and the potential regulation of these effects by hippocampal projections to VMH. Extracellular single-unit discharges were recorded in VHM following administration of nesfatin-1. The projection of nerve fibers and expression of nesfatin-1 were assessed by retrograde tracing and fluoro-immunohistochemical staining, respectively. Results showed that there were GD-responsive neurons in VMH; Nesfatin-1 administration and electrical stimulation of hippocampal CA1 sub-region altered the firing rate of these neurons. These changes could be partially blocked by pretreatment with the non-selective CRF antagonist astressin-B or an antibody to NUCB2/nesfatin-1. Electrolytic lesion of CA1 hippocampus reduced the effects of nesfatin-1 on VMH GD-responsive neuronal activity. These studies suggest that nesfatin-1 plays an important role in GD-responsive neuronal activity through interactions with CRF signaling pathways in VMH. The hippocampus may participate in the modulation of nesfatin-1-mediated effects in VMH., H. Feng, Q. Wang, F. Guo, X. Han, M. Pang, X. Sun, Y. Gong, L. Xu., and Obsahuje bibliografii