Protoplasma - Alkyl hydroperoxide reductase subunit F (AhpF) is a well-known flavoprotein that transfers electrons from pyridine nucleotides to the peroxidase protein AhpC via redox-active... 相似文献
The nucleus-encoded 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) regulates cyclophilin D (cypD) in the mitochondrial matrix. CypD regulates opening of mitochondrial permeability transition pores. Both mechanisms may be affected by amyloid β peptides accumulated in mitochondria in Alzheimer's disease (AD). In order to clarify changes occurring in brain mitochondria, we evaluated interactions of both mitochondrial proteins in vitro (by surface plasmon resonance biosensor) and detected levels of various complexes of 17β-HSD10 formed in vivo (by sandwich ELISA) in brain mitochondria isolated from the transgenic animal model of AD (homozygous McGill-R-Thy1-APP rats) and in cerebrospinal fluid samples of AD patients. By surface plasmon resonance biosensor, we observed the interaction of 17β-HSD10 and cypD in a direct real-time manner and determined, for the first time, the kinetic parameters of the interaction (ka 2.0?×?105 M1s?1, kd 5.8?×?104 s?1, and KD 3.5?×?10–10 M). In McGill-R-Thy1-APP rats compared to controls, levels of 17β-HSD10–cypD complexes were decreased and those of total amyloid β increased. Moreover, the levels of 17β-HSD10–cypD complexes were decreased in cerebrospinal fluid of individuals with AD (in mild cognitive impairment as well as dementia stages) or with Frontotemporal lobar degeneration (FTLD) compared to cognitively normal controls (the sensitivity of the complexes to AD dementia was 92.9%, that to FTLD 73.8%, the specificity to AD dementia equaled 91.7% in a comparison with the controls but only 26.2% with FTLD). Our results demonstrate the weakened ability of 17β-HSD10 to regulate cypD in the mitochondrial matrix probably via direct effects of amyloid β. Levels of 17β-HSD10–cypD complexes in cerebrospinal fluid seem to be the very sensitive indicator of mitochondrial dysfunction observed in neurodegeneration but unfortunately not specific to AD pathology. We do not recommend it as the new biomarker of AD.
Treatment of helper T (Th) cells with saponins from soy bean and mung bean prevented their activation by inhibiting cell proliferation and cytokine secretion. However, the saponins did not affect the expression of major histocompatibility complex class II (Ab) and co-stimulatory molecule (CD86) on professional antigen-presenting cells. Instead, the saponins directly inhibited Th cell proliferation by blocking the G1 to S phase cell cycle transition. Moreover, blocking of the cell cycle by the saponins was achieved by decreased expression of cyclin D1 and cyclin E, and constitutive expression of p27KIP1. Saponins also increased stability of p27KIP1 in Th cells after antigenic stimulation. 相似文献
Amyloid β-peptide (Aβ) pathology is an invariant feature of Alzheimer disease, preceding any detectable clinical symptoms by more than a decade. To this end, we seek to identify agents that can reduce Aβ levels in the brain via novel mechanisms. We found that (20S)-Rg3, a triterpene natural compound known as ginsenoside, reduced Aβ levels in cultured primary neurons and in the brains of a mouse model of Alzheimer disease. The (20S)-Rg3 treatment induced a decrease in the association of presenilin 1 (PS1) fragments with lipid rafts where catalytic components of the γ-secretase complex are enriched. The Aβ-lowering activity of (20S)-Rg3 directly correlated with increased activity of phosphatidylinositol 4-kinase IIα (PI4KIIα), a lipid kinase that mediates the rate-limiting step in phosphatidylinositol 4,5-bisphosphate synthesis. PI4KIIα overexpression recapitulated the effects of (20S)-Rg3, whereas reduced expression of PI4KIIα abolished the Aβ-reducing activity of (20S)-Rg3 in neurons. Our results substantiate an important role for PI4KIIα and phosphoinositide modulation in γ-secretase activity and Aβ biogenesis. 相似文献
Elevated and chronic nitrogen (N) deposition to N-limited terrestrial ecosystems can lead to ‘N saturation’, with resultant ecosystem damage and leaching of nitrate (NO3?) to surface waters. Present-day N deposition, however, is often a poor predictor of NO3? leaching, and the pathway of the ecosystem transition from N-limited to N-saturated remains incompletely understood. The dynamics of N cycling are intimately linked to the associated carbon (C) and sulphur (S) cycles. We hypothesize that N saturation is associated with shifts in the microbial community, manifest by a decrease in the fungi-to-bacteria ratio and a transition from N to C limitation. Three mechanisms could lead to lower amount of bioavailable dissolved organic C (DOC) for the microbial community and to C limitation of N-rich systems: (1) Increased abundance of N for plant uptake, causing lower C allocation to plant roots; (2) chemical suppression of DOC solubility by soil acidification; and (3) enhanced mineralisation of DOC due to increased abundance of electron acceptors in the form of ${{\text{SO}}_{ 4}}^{ 2-}$ SO 4 2 ? and NO3? in anoxic soil micro-sites. Here we consider each of these mechanisms, the extent to which their hypothesised impacts are consistent with observations from intensively-monitored sites, and the potential to improve biogeochemical models by incorporating mechanistic links to the C and S cycles. 相似文献
Capsule The highest densities of Meadow Pipits in Central Europe are found in lowland and upland wet meadows.Aims To create a large-scale predictive model of Meadow Pipit density.Methods We analysed factors affecting the density of the Meadows Pipit in Poland using data from 777?×?1?km study plots and a set of 22 environmental variables, including agriculture intensification and habitat-specific plant species as classifiers of meadow types. Predictors were selected using variation inflation factor, then related to species density data using generalized additive models.Results The best-supported model included 11 variables and was clearly better (Akaike information criterion weight?=?0.47) than other models. The density of the Meadow Pipit reaches its highest levels on large areas of extensively used wet meadows as well as pastures where livestock graze and which show high photosynthetic activity in April.Conclusion Some aspects of the environment that were not identified from remote sensing data were vital for determining relatively high density. Conservation efforts for preserving Meadow Pipit populations should focus on maintaining wet meadows and extensively grazed pastures. Given the results, the Meadows Pipit may be classified as a good indicator of traditional agriculture. 相似文献