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Phytochrome A (phyA) is the primary photoreceptor mediating deetiolation under far-red (FR) light, whereas phyB predominantly regulates light responses in red light. SUPPRESSOR OF PHYA-105 (SPA1) forms an E3 ubiquitin ligase complex with CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), which is responsible for the degradation of various photomorphogenesis-promoting factors, resulting in desensitization to light signaling. However, the role of phyB in FR light signaling and the regulatory pathway from light-activated phytochromes to the COP1-SPA1 complex are largely unknown. Here, we confirm that PHYB overexpression causes an etiolation response with reduced ELONGATED HYPOCOTYL5 (HY5) accumulation under FR light. Notably, phyB exerts its nuclear activities and promotes seedling etiolation in both the presence and absence of phyA in response to FR light. PhyB acts upstream of SPA1 and is functionally dependent on it in FR light signaling. PhyB interacts and forms a protein complex with SPA1, enhancing its nuclear accumulation under FR light. During the dark-to- FR transition, phyB is rapidly imported into the nucleus and facilitates nuclear SPA1 accumulation. These findings support the notion that phyB plays a role in repressing FR light signaling. Activity modulation of the COP1-SPA E3 complex by light-activated phytochromes is an effective and pivotal regulatory step in light signaling. [ABSTRACT FROM AUTHOR]

Abstract: Dendroaspis natriuretic peptide (DNP), a newly-described natriuretic peptide, relaxes gastrointestinal smooth muscle. L-type calcium channel currents play an important role in regulating smooth muscle contraction. The effect of DNP on L-type calcium channel currents in gastrointestinal tract is still unclear. This study was designed to investigate the effect of DNP on barium current (IBa) through the L-type calcium channel in gastric antral myocytes of guinea pigs and cGMP-pathway mechanism. The whole-cell patch-clamp technique was used to record L-type calcium channel currents. The content of cGMP in guinea pig gastric antral smooth muscle and perfusion solution was measured using radioimmunoassay. DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in perfusion medium. DNP concentration-dependently inhibited IBa in freshly isolated guinea pig gastric antral circular smooth muscle cells (SMCs) of guinea pigs. DNP-induced inhibition of IBa was partially blocked by LY83583, an inhibitor of guanylate cyclase. KT5823, a cGMP-dependent protein kinase (PKG) inhibitor, almost completely blocked DNP-induced inhibition of IBa. However, DNP-induced inhibition of IBa was potentiated by zaprinast, an inhibitor of cGMP-sensitive phosphodiesterase. Taken together, DNP inhibits L-type calcium channel currents via pGC–cGMP–PKG-dependent signal pathway in gastric antral myocytes of guinea pigs. [ABSTRACT FROM AUTHOR]

Abstract: Dendroaspis natriuretic peptide (DNP), a newly-described natriuretic peptide, plays an inhibitory role in smooth muscle motility of the gastrointestinal tract. However, the effect of DNP on delayed rectifier potassium currents I K(V) is still unclear. In this study, we sought to investigate the effect of DNP on I K(V) and its mechanism in gastric antral circular smooth muscle cells using the whole-cell patch-clamp technique. DNP significantly inhibited I K(V) in a concentration-dependent manner. LY83583 (1 µmol/l), a guanylate cyclase inhibitor, significantly impaired DNP-induced inhibition of I K(V). Moreover, DNP-induced inhibition in I K(V) was potentiated by the cyclic guanosine monophosphate (cGMP) sensitive phosphoesterase inhibitor zaparinast (0.1 µmol/l). DNP-induced inhibition of I K(V) was completely blocked by KT5823, an inhibitor of cGMP-dependent protein kinase G(PKG), but not affected by KT-5720, a PKA-specific inhibitor. Taken together, our results suggest that DNP inhibits I K(V) via the cGMP/PKG-dependent signaling axis instead of the cAMP/PKA pathway. [Copyright &y& Elsevier]

AbstractSmall-ubiquitin modifier (SUMO) has emerged as a novel modification system that governs the activities of a wide spectrum of protein substrates. SUMO-specific proteases (SENP) are of particular interest, as they are responsible for both the maturation of SUMO precursors and for their deconjugation. The interruption of SENPs has been implicated in embryonic defects and carcinoma cells, indicating that a proper balance of SUMO conjugation and deconjugation is crucial. Recent advances in molecular and cellular biology have highlighted the distinct subcellular localization, and endopeptidase and isopeptidase activities of SENPs, suggesting that they are nonredundant. A better understanding of the molecular basis of SUMO recognition and hydrolytic cleavage has been obtained from the crystal structures of SENP–substrate complexes. While a number of proteomic studies have shown an upregulation of sumoylation, attention is now increasingly being directed towards the regulatory mechanism of sumoylation, in particular the oxidative effect. Findings on the oxidation-induced intermolecular disulfide of E1-E2 ligases and SENP1/2 have improved our understanding of the mechanism by which modification is switched up or down. More intriguingly, a growing body of evidence suggests that sumoylation cross-talks with other modifications, and that the upstream and downstream signaling pathway is co-regulated by more than one modifier. Antioxid. Redox Signal.11, 1453–1484. [ABSTRACT FROM AUTHOR]

Tackles the role of protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) in modulating cellular levels of phosphotyrosine in resting T cells. Overview of T cell receptor signal transduction; Regulation of nonreceptor PTK by tyrosine phosphorylation; Role of PTP CD45 in regulating immune cell function.

To investigate the effect of formononetin on phosphatase and tensin homology deleted on chromosome ten/protein kinase B signaling pathway and angiogenesis of transplanted tumor in nude mice with breast cancer cells. Nude mice with breast cancer cell transplanted tumors were established and randomly divided into control group, low (0.1 mg/g) and medium (0.2 mg/g) doses of formononetin, high (0.4 mg/g) and taxol (10 µg/g) groups, after grouping treatment, the transplanted tumor volumes of nude mice in each group were measured; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was used to detect the apoptosis of transplanted tumor cells; the angiogenesis (proportion of cluster of differentiation 31 positive cells) of transplanted tumors was detected by immunohistochemical staining; serum vascular endothelial growth factor levels in nude mice were detected by enzyme-linked immunosorbent assay; the expressions of vascular endothelial growth factor and phosphatase and tensin homology deleted on chromosome ten/protein kinase B pathway related proteins in transplanted tumors were detected by Western blot assay. Compared to the control group, the volumes of transplanted tumors, the proportion of cluster of differentiation 31 positive cells, serum vascular endothelial growth factor levels, vascular endothelial growth factor protein expression, and phosphorylated-protein kinase B/protein kinase B of nude mice were decreased, while the proportion of apoptotic cells and phosphatase and tensin homology deleted on chromosome ten protein expression were increased in a dose-dependent manner (p<0.05) in low, medium and high doses of formononetin or taxol groups; however, there were no differences in all indexes between taxol group and high dose group of formononetin (p>0.05). Formononetin up-regulates phosphatase and tensin homology deleted on chromosome ten expression, decreases protein kinase B phosphorylation and inhibits transplanted tumor growth and angiogenesis of transplanted tumor in nude mice with breast cancer cells. [ABSTRACT FROM AUTHOR]

Abstract Rheumatoid arthritis (RA) represents a type of autoimmune disease that mainly affect the joints due to persistent synovitis. Eosinophils were Th2 effector cells that have been shown to have anti-inflammatory role recently. In this study, we aimed to investigate the effects of eosinophils transfer on arthritis and underlying mechanisms. DBA/1 mice were induced with collagen-induced arthritis (CIA) and treated with purified eosinophils at different time points. We showed that eosinophils transfer attenuated arthritis in CIA mice. Meanwhile, TNF-α, IL-6, IL-12 and iNOS levels were decreased whereas TGF-β, IL-10, IL-13 and Arg1 levels were increased after eosinophil transfer. In vitro stimulation of bone marrow-derived macrophage (BMDM) with LPS and IFN-γ induced high expression of CD68, iNOS, TNF-α, IL-6, and IL-12, while treatment with eosinophils downregulated their expression levels. Furthermore, high levels of p-IκB and p-P38 expression in BMDM induced by LPS and IFN-γ could be suppressed by eosinophil treatment, and a P38 or IκB inhibitor accelerated the effect of eosinophils on macrophage polarization. Our results demonstrate that eosinophils exert anti-inflammatory effects in arthritis by inducing M2 macrophage polarization via inhibiting the IκB/P38 MAPK signaling pathway. Highlights • Eosinophils attenuate inflammation and bone destruction in collagen-induced arthritic mice. • Eosinophils shift macrophage polarization into M2 phenotype in IL-4/IL-13 dependent manner. • Increased synovial fibroblast viability and RANKL expression induced by M1 macrophages was counteracted by eosinophils. [ABSTRACT FROM AUTHOR]

Common wheat, Triticum aestivum, is the most widely grown staple crop worldwide. To catch up with the increasing global population and cope with the changing climate, it is valuable to breed wheat cultivars that are tolerant to abiotic or shade stresses for density farming. Arabidopsis LONG HYPOCOTYL IN FAR-RED 1 (AtHFR1), a photomorphogenesis-promoting factor, is involved in multiple light-related signaling pathways and inhibits seedling etiolation and shade avoidance. We report that overexpression of AtHFR1 in wheat inhibits etiolation phenotypes under various light and shade conditions, leading to shortened plant height and increased spike number relative to non-transgenic plants in the field. Ectopic expression of AtHFR1 in wheat increases the transcript levels of TaCAB and TaCHS as observed previously in Arabidopsis, indicating that the AtHFR1 transgene can activate the light signal transduction pathway in wheat. AtHFR1 transgenic seedlings significantly exhibit tolerance to osmotic stress during seed germination compared to non-transgenic wheat. The AtHFR1 transgene represses transcription of TaFT1, TaCO1, and TaCO2, delaying development of the shoot apex and heading in wheat. Furthermore, the AtHFR1 transgene in wheat inhibits transcript levels of PHYTOCHROME-INTERACTING FACTOR 3-LIKEs (TaPIL13, TaPIL15-1B, and TaPIL15-1D), downregulating the target gene STAYGREEN (TaSGR), and thus delaying dark-induced leaf senescence. In the field, grain yields of three AtHFR1 transgenic lines were 18.2–48.1% higher than those of non-transgenic wheat. In summary, genetic modification of light signaling pathways using a photomorphogenesis-promoting factor has positive effects on grain yield due to changes in plant architecture and resource allocation and enhances tolerances to osmotic stress and shade avoidance response. [ABSTRACT FROM AUTHOR]

It is well known that natriuretic peptides (NPs) are involved in the regulation of gastrointestinal motility. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal motility and gastrointestinal dyskinesia is one of the important digestive tract symptoms of depression. However, it is unclear whether they are involved in depression-induced loss of ICC. The aim of the present study was to investigate the relationship between the natriuretic peptide signaling pathway and depression-induced loss of gastric ICC in depressed rats. These results showed that the expression of c-kit and stem cell factor (SCF) in smooth muscle layers of stomach were down-regulated in depressed rats at the mRNA and protein levels. The expression of natriuretic peptide receptor (NPR)-A, B and C were up-regulated in the stomach of depressed rats at the mRNA and protein levels. NPR-A, B and C can significantly decrease the expression of SCF to treat cultured gastric smooth muscle cells (GSMCs) obtained from normal rats with different concentrations of C-type natriuretic peptide (CNP). Pretreatment of cultured GSMCs with 8-Brom-cGMP (8-Br-cGMP, a membrane permeable cGMP analog), cANF (a specific NPR-C agonist) and CNP (10−6 mol/L) demonstrated that 8-Br-cGMP had a similar effect as CNP, but treatment with cANF did not. The results of the methyl thiazolyl tetrazolium bromide (MTT) assay indicated that high concentrations of cANF (10−6 mol/L) restrained the proliferation of cultured GSMCs. Taken together, these results indicate that the up-regulation of the NPs/NPR-C and NPs/NPR-A, B/cGMP signaling pathways may be involved in depression-induced loss of gastric ICC. [ABSTRACT FROM AUTHOR]