BFAR与p75NTR的蛋白相互作用抑制p75NTR信号转导

p75NTR是低亲和力的神经生长因子受体,能与高亲和力受体TrkA协同作用促进细胞增殖,也能与细胞内配体结合介导死亡信号通路,诱导细胞凋亡.为了探讨p75NTR功能的调控机制,本文利用膜蛋白酵母双杂交技术从人胎脑cDNA文库中筛选到一个新的p75NTR相互作用蛋白--BFAR.通过对酵母的共转化、GST pull-down和免疫共沉淀实验,证实了p75NTR与BFAR蛋白在体内外相互作用的特异性.荧光共定位实验发现,两者可共定位于细胞质中.此外,荧光素酶检测实验表明,共转染p75NTR和BFAR能够抑制p75NTR介导的NFκB和JNK信号通路.细胞周期实验发现,BFAR在PC-12细胞和HEK293T细胞中的高表达使细胞周期中的G2/M期细胞数增加,S期细胞数量减少,而G0/G1期细胞数无显著差异.     

Discovery of novel inhibitors of LEDGF/p75-IN protein–protein interactions

Human lens epithelium-derived growth factor (LEDGF)/p75 plays an important role in the HIV life cycle by stimulating integrase (IN)-led viral DNA integration into cellular chromosomes. Mechanistic studies show the majority of IN inhibitors chelate magnesium ions in the catalytic active site, a region topologically distant from the LEDGF/p75 binding site. Compounds disrupting the formation of LEDGF/p75 and IN complexes serve as a novel mechanistic approach different from current antiretroviral therapies. We previously built pharmacophore models mimicking LEDGF/p75 residues and identified four classes of LEDGF/p75-IN inhibitors. Substructure and similarity searches yielded additional LEDGF/p75-IN inhibitors containing an acylhydrazone moiety. The most potent of the acylhydrazones inhibited LEDGF/p75-IN interaction with an IC₅₀ value of 400 nM. We explored structure–activity relationships (SAR) and identified new acylhydrazones, hydrazines, and diazenes as lead molecules for further optimization. Two lead LEDGF/p75-IN inhibitors showed antiviral activity.     

p75NTR介导神经细胞凋亡研究进展

在神经发育过程中,神经营养因子通过其低亲和力受体p75NTR与高亲和力受体Trk的介导,在神经元的存活、分化与髓鞘形成中发挥着重要的作用;与存活、生长这些“正性”信号相反,p75NTR也介导受损后及新生神经元凋亡这一“负性”信号。一直以来,p75NTR是如何介导这些截然相反的功能仍不清楚,尤其是何时引起凋亡,其机制如何更是所知甚少。近来,随着s-p75NTR、proNGF、sortilin复合受体等的发现,其中的一些机制开始有所明朗。本文就p75NTR介导神经元凋亡的研究进展做一综述。     

Serum concentrations of TNF-α, sTNF-R p55 and p75 and post-traumatic stress in German soldiers

Growing evidence suggests involvement of the tumor necrosis factor (TNF)-α system in the pathophysiology of psychiatric disorders. Research into post-traumatic stress disorder (PTSD) has investigated serum levels of TNF-α, but not to date its soluble receptors sTNF-R p55 and sTNF-R p75. We examined serum levels of TNF-α, sTNF-R p55 and sTNF-R p75 in 135 male German soldiers 70 of whom had been deployed abroad and 65 in Germany only. Post-traumatic stress symptoms were measured using the Post-traumatic Stress Diagnostic Scale (PDS) and the Trier Inventory for the Assessment of Chronic Stress (TICS). Correlational analysis controlling for multiple testing, showed no significant Spearman rank correlations between PDS or TICS scores and serum levels of TNF-α, sTNF-R p55 or sTNF-R p75, either in the full sample or in the group of soldiers who had been deployed abroad. ANCOVAs showed no significant differences between soldiers with or without a PDS-derived diagnosis of PTSD, or between soldiers with or without deployment abroad, after controlling for age, smoking and body mass index (BMI). These results suggest that the TNF-α system, as reflected by TNF-α, sTNF-R p55 and sTNF-R p75 serum levels, does not play a major role in the pathophysiology and development of PTSD symptoms as measured by the PDS and the TICS. However, several methodological and contextual issues have to be considered.     

p75NTR Antagonistic Cyclic Peptide Decreases the Size of β Amyloid-Induced Brain Inflammation

Amyloid beta (Aβ) was shown to bind the 75 kD neurotrophin receptor (p75^NTR) to induce neuronal death. We synthesized a p75^NTR antagonistic peptide (CATDIKGAEC) that contains the KGA motif that is present in the toxic part of Aβ and closely resembles the binding site of NGF for p75^NTR. In vivo injections of Aβ into the cerebral cortex of B57BL/6 mice together with the peptide produced significantly less inflammation than simultaneous injections of Aβ and a control (CKETIADGAC, scrambled) peptide injected into the contralateral cortex. These data suggest that blocking the binding of Aβ to p75^NTR may reduce neuronal loss in Alzheimer’s disease.     

Proteolytic processing of the p75 neurotrophin receptor: A prerequisite for signalling?

The common neurotrophin receptor (p75(NTR) ) regulates various functions in the developing and adult nervous system. Cell survival, cell death, axonal and growth cone retraction, and regulation of the cell cycle can be regulated by p75(NTR) -mediated signals following activation by either mature or pro-neurotrophins and in combination with various co-receptors, including Trk receptors and sortilin. Here, we review the known functions of p75(NTR) by cell type, receptor-ligand combination, and whether regulated intra-membrane proteolysis of p75(NTR) is required for signalling. We highlight that the generation of the intracellular domain fragment of p75(NTR) is associated with many of the receptor functions, regardless of its ligand and co-receptor interactions.     

p75受体信号转导途径的研究进展

神经生长因子 (ｎｅｒｖｅｇｒｏｗｔｈｆａｃｔｏｒ,ＮＧＦ)通过与两种受体结合而发挥作用。一种是高亲和性受体ＴｒｋＡ受体 ,它是由原癌基因Ｔｒｋ编码的蛋白质酪氨酸激酶 ;另一种是低亲和性受体ｐ75,它以相同的亲和力与神经营养素 (ｎｅｕｒｏｔｒｏｐｈｉｎ ,ＮＴ)家族的各成员结合 ,因此被称为神经营养素受体ｐ75(ｐ75ＮＴＲ)。ＮＧＦ与ＴｒｋＡ受体结合后发挥其促进神经细胞生长和存活的作用 ,而近年来发现ｐ75受体在特定条件下却能够诱导某些神经细胞和胶质细胞的凋亡 ,由于ｐ75ＮＴＲ的这一作用 ,它受到越来越多的关注。1 .ｐ75Ｎ…     

The Effects of Transmembrane Sequence and Dimerization on Cleavage of the p75 Neurotrophin Receptor by γ-Secretase

Cleavage of transmembrane receptors by γ-secretase is the final step in the process of regulated intramembrane proteolysis (RIP) and has a significant impact on receptor function. Although relatively little is known about the molecular mechanism of γ-secretase enzymatic activity, it is becoming clear that substrate dimerization and/or the α-helical structure of the substrate can regulate the site and rate of γ-secretase activity. Here we show that the transmembrane domain of the pan-neurotrophin receptor p75^NTR, best known for regulating neuronal death, is sufficient for its homodimerization. Although the p75^NTR ligands NGF and pro-NGF do not induce homerdimerization or RIP, homodimers of p75^NTR are γ-secretase substrates. However, dimerization is not a requirement for p75^NTR cleavage, suggesting that γ-secretase has the ability to recognize and cleave each receptor molecule independently. The transmembrane cysteine 257, which mediates covalent p75^NTR interactions, is not crucial for homodimerization, but this residue is required for normal rates of γ-secretase cleavage. Similarly, mutation of the residues alanine 262 and glycine 266 of an AXXXG dimerization motif flanking the γ-secretase cleavage site within the p75^NTR transmembrane domain alters the orientation of the domain and inhibits γ-secretase cleavage of p75^NTR. Nonetheless, heteromer interactions of p75^NTR with TrkA increase full-length p75^NTR homodimerization, which in turn potentiates the rate of γ-cleavage following TrkA activation independently of rates of α-cleavage. These results provide support for the idea that the helical structure of the p75^NTR transmembrane domain, which may be affected by co-receptor interactions, is a key element in γ-secretase-catalyzed cleavage.     

p75神经营养素受体介导的信号传递

ｐ７５神经营养素受体除可增强神经营养素与Ｔｒｋｓ受体作用外,还可与神经营养素结合启动另外的信号传递通路。首先,活化的ｐ７５＾ＮＴＲ可激活胞内的转录因子ＮＦ－ｋＢ;其次,ｐ７５＾ＮＴＲ与神经营养素结合,可促进神经细胞内鞘磷脂的水解、神经酰胺的释放,导致细胞程序性死亡。此外,ｐ７５＾ＮＴＲ还表现出对配体的选择性,而且它与Ｔｒｋｓ之间存在着相互作用的关系。     

实验性铅中毒对大鼠海马p75基因表达的影响

目的　探讨铅对海马 p75基因表达的影响。方法　采用RT PCR方法 ,半定量分析铅对大鼠海马组织NGFmRNA表达的变化。以地高辛标记的p75cDNA为探针 ,采用原位杂交方法观察铅对大鼠海马 p75mRNA表达的影响。结果　与对照组相比 ,大鼠以 1%醋酸铅经口染毒 8周 ,海马组织 p75mRNA的表达量明显下降 (P <0 0 1)。结论　铅可影响海马 p75基因的表达。     

Identification of old drugs as potential inhibitors of HIV-1 integrase – human LEDGF/p75 interaction via molecular docking

Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, human protein Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. LEDGF/p75-HIV-1 IN interaction represents an attractive target for anti-HIV therapy. In this study, approved drugs were investigated for the finding of potential inhibitors on this target. Via molecular docking against the LEDGF/p75-binding pocket of HIV-1 IN, 26 old drugs were selected from the DrugBank and purchased for bioassays. Among them, eight, namely Atorvastatin, Bumetanide, Candesartan, Carbidopa, Diclofenac, Diflunisal, Eprosartan, and Sulindac, were identified as potential inhibitors of LEDGF/p75- HIV-1 IN interaction, whose IC₅₀ values ranged from 6.5?μM to 36.8?μM. In addition, Atorvastatin was previously reported to block HIV-1 replication and may have an important implication for the treatment of AIDS. Our results suggested a mechanism of action for the anti-HIV effects of Atorvastatin. This work provides a new example of inhibitors targeting protein-protein interaction and confirmed that old drugs were valuable sources for antiviral drug discovery.     

TRAF6 and p62 inhibit amyloid β-induced neuronal death through p75 neurotrophin receptor

Amyloid β (Aβ) aggregates are the primary component of senile plaques in Alzheimer disease (AD) patient’s brain. Aβ is known to bind p75 neurotrophin receptor (p75^NTR) and mediates Aβ-induced neuronal death. Recently, we showed that NGF leads to p75^NTR polyubiquitination, which promotes neuronal cell survival. Here, we demonstrate that Aβ stimulation impaired the p75^NTR polyubiquitination. TRAF6 and p62 are required for polyubiquitination of p75^NTR on NGF stimulation. Interestingly, we found that overexpression of TRAF6/p62 restored p75^NTR polyubiquitination upon Aβ/NGF treatment. Aβ significantly reduced NF-κB activity by attenuating the interaction of p75^NTR with IKKβ. p75^NTR increased NF-κB activity by recruiting TRAF6/p62, which thereby mediated cell survival. These findings indicate that TRAF6/p62 abrogated the Aβ-mediated inhibition of p75^NTR polyubiquitination and restored neuronal cell survival.     

TRAF6 and p62 inhibit amyloid β-induced neuronal death through p75 neurotrophin receptor

Amyloid β (Aβ) aggregates are the primary component of senile plaques in Alzheimer disease (AD) patient’s brain. Aβ is known to bind p75 neurotrophin receptor (p75^NTR) and mediates Aβ-induced neuronal death. Recently, we showed that NGF leads to p75^NTR polyubiquitination, which promotes neuronal cell survival. Here, we demonstrate that Aβ stimulation impaired the p75^NTR polyubiquitination. TRAF6 and p62 are required for polyubiquitination of p75^NTR on NGF stimulation. Interestingly, we found that overexpression of TRAF6/p62 restored p75^NTR polyubiquitination upon Aβ/NGF treatment. Aβ significantly reduced NF-κB activity by attenuating the interaction of p75^NTR with IKKβ. p75^NTR increased NF-κB activity by recruiting TRAF6/p62, which thereby mediated cell survival. These findings indicate that TRAF6/p62 abrogated the Aβ-mediated inhibition of p75^NTR polyubiquitination and restored neuronal cell survival.     

Immunoscintigraphy with biosynthetically-labeled 75Se-antibodies—I. Biodistribution of 75Se-monoclonal antibodies and of free radionuclide

Biosynthetically-radiolabeled MoAbs provide a tool to test whether structural modifications of the MoAbs influence the results of conventional immunoscintigraphy. When biosynthetically-labeled ⁷⁵Se-MoAbs from the Mel-14 hybridoma were injected into mice with melanoma xenografts, the high tumor recovery supported the hypothesis of a structural advantage. The increased excretion of ⁷⁵Se obtained by supplementing the diet of the mice with cold selenium did not reduce the tumor recovery, demonstrating an accumulation of the free radionuclide in normal tissue.     

The p75NTR extracellular domain: A potential molecule regulating the solubility and removal of amyloid-��

Senile plaque composed of amyloid-beta (Aβ) in the brain is one of the hallmarks of Alzheimer disease (AD). Removal of Aβ from the brain is the most important therapeutic strategy for AD. The solubility of Aβ is critical for its endocytosis, transcytosis and removal from the brain. Our recent study has found that the extracellular domain of p75NTR, the neurotrophin receptor, plays an important role in the solubility of Aβ and might be one of the endogenous mechanisms in the regulation of Aβ plaque formation. The physiologically shedded extracellular domain of p75NTR is able to inhibit Aβ aggregation and diasggregate preformed Aβ fibrils, while the full p75NTR expressed on neurites, endothelial cells and smooth muscle cells in blood-brain barrier (BBB) might initiate Aβ endocytosis and degradation, and/or remove Aβ from the brain via BBB. Understanding the roles of p75NTR in the solubility and clearance of Aβ may allow targetting p75NTR as a unique opportunity to develop therapeutic drugs for the prevention and treatment of AD.Key words: Alzheimer disease, amyloid-β, p75NTR, extracellular domain, blood-brain barrier, clearanceSenile plaque in the brain is one of the hallmarks of Alzheimer disease (AD). The main component of the senile plaques is amyloid-beta (Aβ), which is a metabolic product of amyloid precursor protein (APP). The steady-state level of Aβ in the normal brain is maintained by the balance between its production and clearance. However in the AD brain this balance is broken due to either over-production of Aβ or a reduction in Aβ clearance;^1,2 thus Aβ accumulates in the brain and forms amyloid plaques which cause dementia and neurodegeneration in patients. Based on the Aβ hypothesis proposed a decade ago, Aβ plays a causal and pivotal role in the development of AD.³ Therefore, removal of Aβ from the brain is the most important therapeutic strategy for AD.⁴ To reach this goal, it is essential to understand how the Aβ metabolism is regulated in the AD brain. Despite the dramatic progress has been made in the understanding of how Aβ is produced from APP, the mechanisms of Aβ aggregation, metabolism and clearance from the brain remain unclear so far. Only 5% of AD (familial cases) is due to the over-production of Aβ because of mutations in the APP gene or in the APP processing enzymes, while the majority (95%) of so-called sporadic or late-onset AD (LOAD) are likely caused by dysfunctions in Aβ solubility or aggregation, endocytosis, degradation, transcytosis and removal.The solubility of Aβ is critical for its endocytosis, transcytosis and removal from the brain. In AD patients, one of the most consistent biomarkers found so far is the reduction of Aβ level in the cerebral spinal fluid (CSF).⁵ This is the most convincing evidence that there is a reduction in the solubility of Aβ and an increase in the Aβ aggregation and beta-sheet formation in AD patients. In sporadic cases of AD, the polymorphism of the Aβ-binding protein ApoE4 is highly associated with AD. It is known that other variants of ApoE proteins have a higher binding affinity to Aβ than ApoE4. It is likely that ApoE protein plays a critical role in the solubility of Aβ.⁶ The reduction in the Aβ binding ability of ApoE4 may reduce the solubility of Aβ. Thus ApoE protein may act on Aβ keeping it soluble and preventing its aggregation, and ApoE4 variant may reduce Aβ solubility and increase aggregation in the brain. It is not fully understood at this time, what other proteins that might regulate Aβ solubility and prevent its aggregation. Understanding the endogenous mechanism of suppressing Aβ aggregation and enhancing its removal will help to target Aβ for developing disease-modifying drugs.The neurotrophin receptor p75NTR may be such the protein which plays critical roles in the Aβ solubility and prevents Aβ aggregation and deposition in the brain. During the investigation into the functions of p75NTR in the development of AD in a recent study, we have found that the extracellular domain of p75NTR regulates the deposition of Aβ in a mouse model of AD.⁷ In p75NTR gene-knockout APPswe/PS1dE9 mice, soluble Aβ which reflects the steady-state level of Aβ production, is reduced in the brain. The serum Aβ level, which is associated with the level of soluble Aβ in the brain, is also reduced in p75NTR-knockout animals. In comparison, we found that p75NTR knockout increases the insoluble Aβ as reflected by the increased amyloid plaques and formic acid-extracted Aβ levels. Our results indicate that p75NTR may play critical roles in the solubility of Aβ in the brain of AD mice. To test the hypothesis, we have made recombinant extracellular domain-fused with human immunoglobulin Fc fragment and tested its effects in the solubility of Aβ in vitro. We have found that the recombinant extracellular domain of p75NTR has a very strong effect on the solubility of Aβ. It reduces Aβ oligomerization and fibrillization, solubilizes fibrilized Aβ. Most interestingly, when injected into the hippocampus of AD mice, it reduces the number and size of Aβ plaques. Thus, we have clearly demonstrated that the extracellular domain plays an important role in the solubility of Aβ and might be one of endogenous mechanisms in the regulation of Aβ plaque formation in patients.How might p75NTR play a role in the Aβ plaque formation or deposition in AD brain? One of the features of the Aβ pathology is that Aβ exclusively deposits in the neocortex, hippocampus and vessel walls. These areas are also the projection area of p75NTR positive fibers. The close anatomical association between p75NTR expression and Aβ deposition strongly suggests that p75NTR is involved in the initiation and development of Aβ deposition in the brain. Interestingly, we have observed there is a spatial relationship between p75NTR fibers and Aβ plaques in the brain of AD mice. We have found that p75NTR positive neurites locates in the center of compact senile plaques, while p75NTR negative degenerative neurites locate in the outer region of Aβ plaques.⁷ This phenomenon suggests that p75NTR positive neurodegenerative fibers may play a seeding role to initiate the Aβ aggregation and plaque formation. It is known that Aβ can bind to the extracellular domain of p75NTR.⁸ Normally, Aβ-bound p75NTR is likely endocytosed and degraded in the lysosomes, but the degenerated neurites may be abnormal in the endocytosis of the Aβ-p75NTR complex. Thus Aβ which binds to p75NTR on the cell surface may act as seeds to initiate the cascade of Aβ aggregation and beta-sheet formation.On the other hand, the extracellular domain of p75NTR after enzymatic shedding may play a different role than the membranous p75NTR. It is known that the p75NTR extracellular domain is physiologically shedded by TACE to generate a soluble and diffusible factor.⁹ The physiological function of the shedded diffusible extracellular domain of p75NTR remains unknown. During the aging process and during the development of AD, p75NTR expression is upregulated,^10,11 and presumably the production of the diffusible extracellar domain of p75NTR is also increased. The increased extracellular domain of the p75NTR is likely a critical factor to maintain the solubility of Aβ, acting in concert with ApoE and other Aβ-binding proteins such as low-density lipoprotein receptor-related protein-1 (LRP1).¹² Indeed, in our animal experiment, we have found that knockout of p75NTR significantly increases the insoluble Aβ, even though the production of Aβ is reduced in p75NTR knockout neurons.⁷ Our data have provided strong evidence that the brain Aβ deposition and amyloid plaque formation may be mainly due to the decreased Aβ solubility or decreased Aβ clearance.The solubility of Aβ goes hand in hand with the clearance of Aβ because only the solubilized Aβ can be endocytosed and degraded in lysosomes by neurons, microglia and astrocytes, and be transported from the brain to the blood for degradation and clearance.⁴ Whether p75NTR plays any roles in the endocytosis of Aβ and degradation is unclear. Our data of increased Aβ deposition in the brain of p75NTR knockout mice may also be explained by the decreased endocytosis of Aβ via p75NTR. It is likely that p75NTR may play a role in Aβ endocytosis, as p75NTR is a receptor of Aβ and mediates its toxicity in neurons.⁸ p75NTR ligands can trigger a clathrin-dependent endocytosis of both p75NTR and its ligands.¹³ If p75NTR normally mediates Aβ endocytosis, the knockout of p75NTR would reduce the removal of Aβ by endocytosis and lead to the increased deposition in the brain.Normally, p75NTR is also expressed in endothelial cells and smooth muscle cells of blood vessels, vessel-innervating sympathetic and sensory neurons and choroid plexus in the brain.^14,15 This raises the possibility that p75NTR within blood vessels may play a role in transport and trafficking of Aβ from the brain to the blood. It is well known that LRP1 plays important roles in the transport and transcytosis of Aβ and clears Aβ from the brain.¹² LRP1 on the cell-surface of the blood-brain barrier (BBB) can bind, transcytose and transport Aβ from the brain to the blood. p75NTR expressed on the BBB may play similar roles in the removal of Aβ in a similar manner to the Aβ binding proteins, LRP1 and G-glycoprotein, expressed on the BBB. Future studies should test roles of p75NTR in the endocytosis, transcytosis and clearance of Aβ by different cells such as neurons, endothelial cells and smooth muscle cells. The levels of shedded diffusible p75NTR in the brain and blood of AD patients should be determined as a biomarker and correlated with Aβ levels or Aβ plaques to reveal its potential roles in the solubility and clearance of Aβ in AD patients.In summary, our studies have provided strong evidence that p75NTR is an essential molecule to keep the solubility of Aβ during development of AD. We speculate that p75NTR might also play many vital roles in removing Aβ from brain (Fig. 1). However, it is still far from certain how p75NTR regulates the solubility of Aβ and suppresses its deposition in the AD brain. Understanding the roles of p75NTR in the solubility and clearance of Aβ may help using p75NTR as a target to develop therapeutic drugs for the prevention and treatment of AD.Open in a separate windowFigure 1Schematic diagram depicting functions of p75NTR in Aβ solubility and clearance. p75NTR locates on the neurites, epithelial cells and smooth muscle cells of the blood-brain barrier (BBB). Binding of Aβ to p75NTR on neurites may initiate the endocytosis of Aβ and its degradation in the neurons. Shedding of p75NTR from the cell membrane releases the soluble extracellular domain (p75NTR-ECD), which is capable of inhibiting Aβ aggregation and disaggregating preformed Aβ fibrils. p75NTR at BBB might be able to transport Aβ from the brain to blood.     

C-terminal region of human p53 attenuates buffalo p53 N-terminal-specific transactivation of p21 promoter by modulating tetramerization of the protein

Here, we have studied in p53 null H1299 lung carcinoma cells, the dominant-negative effect of human p53 (h-p53) on buffalo p53 (b-p53) induced nuclear transactivation-dependent function. Recently, we have isolated and cloned the full-length cDNA of buffalo p53. Buffalo and human p53 proteins exhibit a high degree of structural and functional similarities. In transiently transfected H1299 cell line b-p53 appeared to be more sensitive to Mdm2-mediated degradation as compared to h-p53, although its ability to transactivate p21 promoter was stronger than that of the human counterpart. This higher transactivation ability of b-p53 was lost in the presence of h-p53 suggesting, a dominant-negative effect of h-p53 on b-p53’s transactivation of p21 promoter. Both human and buffalo p53 proteins could hetero-oligomerize but the b-p53 could tetramerize much faster than the h-p53. A chimeric cDNA construct of human p53 was made where the 1–260 bp N-terminus was replaced with buffalo p53 counterpart and expressed in H1299 cell line. The tetramerization ability of the chimeric p53 protein was comparable to that of h-p53. Properties of b-p53 like stronger p21 transactivation and super sensitivity to Mdm2 mediated degradation were lacking in the chimeric protein. Thus, it is suggested that faster ability of tetramerization as well as higher transactivation property of buffalo p53 is determined by the interplay of N- and C-terminal domains through macromolecular interactions.     

Effect of p,p′ DDT on nitrogen fixation of white clover in volcanic soils of Chile

Summary The effect of increasing concentrations of p,p DDT on dry matter production and nitrogen fixation of white clover (Trifolium repens L.) growing in pots with volcanic soils of the southern region of Chile was studied. The chlorinated insecticides content of the soils ranged from low to very high (>20 mg/kg), being associated with the amount of insecticide applied. A detrimental effect of medium and high levels of DDT on growth, dry matter production and N-accumulation of clover was observed. The effects on nodulation and nitrogenase activity were smaller. These effects were higher when nutrient solutions were used instead of soil, because of the protective effects of soil colloids.

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Resumen Se estudió el efecto de concentraciones crecientes de p,p DDT sobre la producción y parámetros de fijación de N del trébol blanco (Trifolium repens L.) en condiciones de invernadero en suelos volcánicos de la zona sur de Chile. Los contenidos de insecticidas clorados de los suelos de la región son desde bajos hasta muy altos (>20 mg/kg), dependiendo de las aplicaciones. Se apreció un efecto depresivo del DDT a dosis medias y altas sobre el crecimiento, producción de materia seca y N-acumulado del trébol y un efecto menor sobre nodulación y actividad nitrogenásica. Estos efectos fueron más acentuados cuando se trabajó con soluciones nutritivas que con suelo, debido a la protección ejercida por los coloides del suelo.

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Résumé On a étudié l'effet de concentrations croissantes de p,p-DDT sur la production de matière sèche et sur la fixation de l'azote par le trèfle blanc (Trifolium repens L.) cultivé en serre sur des échantillons de sols volcaniques du sud du Chili. Dans les sols de cette région, la teneur en résidus d'insecticides chlorés varie entre <1 et >20 mg/kg suivant le niveau des prelévements. Le DDT inhibe la croissance, la production de matière sèche et l'accumulation d'azote par le trèfle. De plus, nous avons constaté un effet secondaire sur la nodulation et l'activité nitrogénasique. Ces effets sont plus marqués lorsqu'on utilise des solutions nutritives au lieu de terre, ce qui est dû à une protection éxercée par les colloides du sol.