PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Kennedy pathway”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Harnessing probiotics to combat nonylphenol toxicity: a multiomics approach of gut microbiome remodelling in Silurus meridionalis.

BACKGROUND: As a ubiquitous environmental endocrine disruptor, nonylphenol (NP) threatens aquatic organisms, driving the need for sustainable mitigation strategies. While probiotics represent promising eco-friendly supplements, their molecular mechanisms against NP toxicity remain unclear. In this study, S. meridionalis received 7-week of probiotic (Bacillus subtilis and Lactobacillus acidophilus) pretreatment followed by 15 days of NP exposure. Integrated metagenomics, transcriptomics, and metabolomics analyses, with Reverse transcription quantitative real-time PCR (RT‒qPCR) and Enzyme-linked immunosorbent assay (ELISA) validation, were performed to elucidate microbial, genetic and metabolic responses. Growth performance, including the specific growth rate (SGR) and weight gain rate (WGR), was concurrently assessed. RESULTS: NP exposure significantly suppressed WGR and SGR, and induced gut microbiota dysbiosis alongside and lipid metabolism disorders in S. meridionalis. Probiotic pretreatment effectively reversed these toxic effects and restored the inhibited WGR and SGR. Multiomics integration revealed that the protective effects of probiotics were mediated by a coherent "microbe-host" co-metabolism network across 3 progressive layers: (1) Microbial Remodelling: in which beneficial taxa (e.g., Bacteroides eggerthii and Cetobacterium sp.) were enriched, and the functional capacity for short-chain fatty acid (SCFA) synthesis and ethanolamine metabolism was enhanced; (2) Host Gene Regulation: in which key lipid metabolism genes (ek1, cept1, ept1, mogat2, and abcg2a) were upregulated, and lipase activity was restored; and (3) Metabolic Pathway Activation and Physiological Repair: in which the activity of the NP-suppressed Kennedy pathway was reactivated, thereby promoting phosphatidylethanolamine (PE) and phosphatidylcholine (PC) synthesis and ultimately restoring gut barrier function. These results were further were corroborated by RT‒qPCR and ELISA. CONCLUSION: This study systematically elucidated that probiotics alleviated NP toxicity by remodelling a "microbiota-host Kennedy pathway gene-metabolite (PE and PC)-growth performance" regulatory network. The key mechanism is the beneficial microbiota activating the host Kennedy pathway and restoring gut phospholipid homeostasis and barrier function. These findings provide a theoretical basis for developing targeted, lipid metabolism focused probiotic feed additives for use in sustainable aquaculture.

Probiotics↗
PubMed1977

Stimulation of renal phospholipid formation during potassium depletion.

Potassium depletion induces increased membrane phospholipid formation and renal growth in rats. To determine the mechanism by which potassium depletion augments phospholipid formation, the metabolism of radioactive choline, a precursor of choline-containing phospholipids, was studied in renal slices. Cortical and medullary tissue from potassium-depleted and control animals accumulated extracellular choline and sequentially converted it to phosphorylcholine, cytidine diphosphocholine (CDP-choline), and choline phosphoglyceride, thereby demonstrating that renal cells can utilize the Kennedy pathway for phospholipid synthesis. [14C]Choline uptake into intracellular fluid was increased in cortical slices from potassium-depleted animals. The apparent Km and Vmax of the kinase reaction which converts entering [14C]choline to [14C]phosphorylcholine were unchanged during potassium depletion. The rate of [14C]phosphorylcholine conversion to [14C]CDP-choline was also unchanged. In contrast, the Vmax of [14C]choline phosphoglyceride formation from [14C]CDP-choline was increased, whereas the apparent Km for this reaction was unchanged. These results indicate that increased renal choline phosphoglyceride formation during potassium depletion can occur via the Kennedy pathway and appears to be mediated by increases in choline uptake and the rate of CDP-choline incorporation into phospholipid, the first and last steps of the pathway.

Animals↗
PubMed1979

Amino acid-mediated stimulation of renal phospholipid biosynthesis after acute tubular necrosis.

The mechanism by which amino acid infusion stimulates membrane physpholipid biosynthesis during renal regeneration after mercuric-chloride-induced acute tubular necrosis was studied in the rat. Amino acids can act directly on regenerating renal tissue to enhance net phospholipid synthesis because preincubation of cortical slices with amino acids induced an increase in [14C]-choline incorporation into phospholipid without altering the rate of breakdown. This amino acid stimulation of phospholipid biosynthesis was studied further by measuring [14C]-choline accumulation and its sequential conversion to phosphorylcholine, cytidine diphosphocholine (CDP-choline), and phosphatidylcholine via the Kennedy pathway in regenerating renal tissue. [14C]-Choline accumulation was increased after amino acid infusion, compared to glucose infusion. There were also increments in the Vmax of the choline kinase reaction, which converts entering [14C]-choline into [14C]-phosphorylcholine, and of the cholinephosphotransferase reaction in which [14C]-CDP-choline is incorporated into [14C]-phosphatidylcholine, whereas the apparent Km of each reaction was unchanged. Thus, amino acids infused after tubular necrosis can act directly on regenerating renal cells to increase precursor availability and augment two reactions of the phospholipid biosynthetic pathway.

Acute Kidney Injury↗
PubMed1977

The effect of acute ethanol administration on phosphorylethanolamine uptake and metabolism in rat liver slices.

Double-labelled phosphorylethanolamine with a [32P]//[14IA1 ratio of 1 was incubated in vitro with rat liver slices prepared from control and ethanol-intoxicated rats, and the radioactivity measured at given time intervals in liver ethanolamine, phosphorylethanolamine, phosphatidylethanolamine and phosphatidylcholine. Evidence is presented that after 10 and 15 minutes phosphorylethanolamine enters the slices as an intact molecule, which is directly converted into lipid forms by the Kennedy's pathways. At longer times a hydrolysis of the ester occurs which lowers considerably the theoretical [32P]/[14C]ratio. Fatty liver slices produced by acute ethanol intoxication uptake from the medium more phosphorylethanolamine than controls, and hydrolyze less efficiently than controls the phosphoric ester to ethanolamine and inorganic phosphate.

Animals↗
PubMed1978

[Projections to the inferior olive of the cat. I. Comparisons of input from the dorsal column nuclei, the lateral cervical nucleus, the spino-olivary pathways, the cerebral cortex and the cerebellum].

The present experiments compare the projections from the dorsal column nuclei (DCN), the lateral cervical nucleus (LCN), the spino-olivary pathways (SO), the motor cortex (Ms1) and the cerebellum (CB) to the inferior olive of the cat. A differential labeling strategy was used for these comparisons. It was found that projections from the contralateral DCN and LCN and the ipsilateral SO overlap extensively with each other in the dorsal accessory division of the inferior olive and the caudal half of the medial accessory olive. Projections from the contralateral motor cortex partially overlap these somato-sensory projections but they also extend into the principal division and into the rostral half of the medial accessory olive where other authors have found input from other "motor" sources such as the red n., the globus pallidus and the caudate n. The contralateral cerebellum projects heavily to most of the inferior olive except for a few regions in the caudal portions of the two accessory nuclei. These results show that there is a partial segregation between somatosensory and motor inputs within the inferior olive and that the cerebellar feedback fibers appear to avoid at least parts of those regions where the somatosensory input is heavy. Some of this segregation, particularly within the medial accessory olive and the principal n., correlates with differences in both the olivo-cerebellar connectivity and the cytoarchitecture of these regions. Although the somatosensory and motor inputs are partially segregated, there are also several regions where these inputs overlap. These regions are: (1) an area in the medial half of the rostral portions of the dorsal accessory olive, and (2) a small oval zone in the middle of the caudal half of the medial accessory olive. This overlap provides an anatomical basis for electrophysiological evidence which demonstrates the existence of cells in some of these regions that respond to activation of both the cerebral cortex and the spinal cord (e.g., Crill and Kennedy, '67).

Animals↗
PubMed1977

Direct projections from thalamic intralaminar nuclei to extra-striate visual cortex in the cat traced with horseradish peroxidase.

Thalamic projections to the visual cortex were investigated using the Horseradish peroxidase tracing technique. Besides confirmation of a distinct origin of thalamic projections to striate and extra-striate visual cortex, afferents of the intralaminar nuclei (ILN) to visual cortex were demonstrated. These projections of ILN were shown to be specific in that they terminate in areas 18, 19 and Clare Bishop but not area 17. The coupling of these intralaminar projections on to the extra-striate visual system is considered with respect ot orientation of gaze.

Animals↗
PubMed1977

Expression of Klebsiella pneumoniae nitrogen fixation genes in nitrate reductase mutants of Escherichia coli.

Nitrate reductase (nar) A, B and E mutants of Escherichia coli with plasmids carrying Klebsiella pneumoniae nitrogen fixation (nif) genes reduced acetylene independently of added molybdate, but nar D mutants showed pleiotropic dependence on the concentration of added molybdate for expression of both nar and nif. No complementation of nar mutations by nif occurred; nitrite but not nitrate repressed nif in nar hosts. Derepression of nif occurred in molybdenum-deficient nar D (nif) strains since nitrogenase peptides were present. nifB mutants, thought to have a lesion in the pathway of molybdenum to nitrogenase, as well as nif deletion mutants, had normal nitrate reductase activity.

Enzyme Repression↗
PubMed1975

Superoxide production and electron transport in mitochondrial oxidation of dihydroorotic acid.

Production of superoxide radical during oxidation of dihydroorotate in rat liver mitochondria was not affected by antimycin A, thenoyltrifluoroacetone, or added ubiquinone but was inhibited by orotate, a product inhibitor of dihydroorotate dehydrogenase. It appears likely that superoxide is generated at the primary dehydrogenase. Dihydroorotate dehydrogenase differs from succinate dehydrogenase both in its utilization of ubiquinone and in the mechanism of cytochrome b reduction. Thenoyltrifluoroacetone completely inhibits fumarate synthesis and reduction of cytochrome b by succinate. Formation of orotate is only partially inhibited by thenolytrifluoroacetone and the inhibitor does not prevent reduction of cytochrome b by dihydroorotate. It is proposed that several pathways exist for linkage of the primary dihydrorotate dehydrogenase with the electron transport chain. One route involves electron transfer from ubiquinone to cytochrome c and is inhibited by thenoyltrifluoroacetone. A second route bypasses ubiquinone and is inhibited by antimycin A. A third pathway utilizes both ubiquinone and cytochrome b and is partiayly inhibited by either thenoyltrifluoroacetone or antimycin A.

Animals↗
PubMed1977

Retinal projections in larval, transforming and adult sea lamprey, Petromyzon marinus.

Unilateral enucleations were performed on larval, transforming and adult sea lampreys. Following 5 to 11 days survival, the animals were sacrificed and the brains were processed using a modified Fink-Heimer technique. In larvae, contralateral optic projections were found to the posterior one-third of the dorsal thalamus, the pretectum, and the optic tectum. No ipsilateral projections were present in the larvae. In enucleated transforming and adult lampreys, degenerating axons were observed in the optic chiasm and bilaterally in the optic tracts. Retinal efferents projected bilaterally to a lateral neuropil region ("tractus opticus") in the posterior one-half of the dorsal thalamus. Contralaterally, a conspicuous dorsomedial cell group (lateral geniculate nucleus) also received a projection. Contralateral projections to the superficial layers of the pretectum and optic tectum were observed. Ipsilateral retinal projections to the pretectum and optic tectum in transforming and adult lampreys were restricted to a small zone at the ventrolateral margins of the pretectum and tectum. The changes in distribution of retinofugal projections during transformation appear to be occurring at the same time that the eye differentiates into its adult form.

Animals↗
PubMed1979

Thalamic projections to area 17 in a prosimian primate, Microcebus murinus.

Electrophysiological recording of single neurons was used to describe the representation of visual space in area 17, and the technique of retrograde transport of horseradish peroxidase (HRP) was applied to relate these results to projections from the thalamus in the prosimian primate Microcebus murinus. The visuotopic organization of area 17 was found to resemble that of other primates. On the dorsal surface, the border of area 17 corresponds to the representation of the vertical meridian. Proceeding medially across the surface the location of receptive fields descends along the vertical meridian, while moving caudally receptive fields progress temporally. Most of the dorsolateral surface is devoted to central vision and corresponds to a well developed area centralis. Following HRP injections in striate cortex, columns of labeled cells were found in the dorsal lateral geniculate (dLGN) extending orthogonally across all six layers. These columns run in a general ventrodorsal and caudorostral direction, parallel to a line connecting the cellular discontinuities corresponding to the optic disc. These discontinuities are present in magnocellular layer 1 and parvocellular layers 5 and 6, thus receiving from the nasal retina of the contralateral eye. The representation of the vertical meridian is situated in the ventromedial portion of the dLGN, and the monocular field is represented in the dorsal extremity. Anterior dLGN projects to the calcarine fissure (lower field) and posterior dLGN projects to the ventral surface of the cortex (upper field). Extrageniculate input to area 17 was found to originate from the pulvinar. HRP labeled cells were located in two distinct divisions of this nucleus, the cytoarchitecture of which is described. In addition, projections to occipital cortex were found to arise from the intralaminar nuclei.

Animals↗
PubMed1975

Mapping of functional neural pathways by autoradiographic survey of local metabolic rate with (14C)deoxyglucose.

An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3,4-tetrahydropyrido(3,4-b)indole) in the presence of 5-methyltetrahydrofolic acid. Similarly, N-methyltryptamine and 5-hydroxytryptamine yield 1-methyltryptoline and 5-hydroxytryptoline, respectively. Neither in vitro nor in vivo formation of these compounds by human tissues has been described.

Animals↗
PubMed1978

Functional plasticity in the immature striate cortex of the monkey shown by the [14C]deoxyglucose method.

Autoradiographic representation of the local rates of cerebral glucose utilization and local cerebral functional activity by means of the [14C]deoxyglucose technique reveals the existence of the ocular dominance columns in the striate cortex of the monkey in the first day of life. In contrast to the stability of these columns in more mature brain, monocular deprivation for 3 months from the first day of life results in their complete disappearance and a reversion of the autoradiographic pattern to that seen in animals with normal binocular vision. These results are consistent with a reorganization of the representation of the visual fields of the two eyes in the striate cortex and provide additional evidence of the plasticity of the striate cortex of the monkey in early life.

Animals↗
PubMed1977

Intracellular distribution of enzymes of phospholipid metabolism in several gram-negative bacteria.

Cell-free extracts of Salmonella typhimurium, Serratia marcescens, Enterobacter aerogenes, and Micrococcus cerificans contained the following enzymatic activities related to phospholipid metabolism: cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDP-diglyceride):l-serine O-phosphatidyltransferase (phosphatidylserine synthase), phosphatidylserine decarboxylase, CDP-diglyceride:sn-glycero-3-phosphate phosphatidyltransferase (phosphatidylglycerophosphate synthase), phosphatidylglycerophosphate phosphatase, and CDP-diglyceride hydrolase. The intracellular distribution of these enzymatic activities as determined by sucrose density gradient centrifugation of cell-free extracts was shown to be similar in each species investigated. The phosphatidylserine decarboxylase, phosphatidylglycerophosphate synthase, and CDP-diglyceride hydrolase activities were all associated with the cell envelope fraction, whereas the phosphatidylserine synthase activity was associated mainly with the ribosomal fraction. These enzymatic activities are comparable and have an intracellular distribution similar to those found in Escherichia coli cell-free extracts. Therefore, the pathways established for phospholipid biosynthesis in E. coli can also account for the synthesis of the major phospholipids (phosphatidylethanolamine and phosphatidylglycerol) in several other gram-negative organisms. In addition, the unusual ribosomal association of the phosphatidylserine synthase from E. coli (Raetz and Kennedy, J. Biol. Chem. 247:2008-2014, 1972) appears to be a general property for this activity in several other bacterial species.

Acinetobacter↗
PubMed1976

Metabolic mapping of the primary visual system of the monkey by means of the autoradiographic [14C]deoxyglucose technique.

An autoradiographic technique that employs 2-[14-C]deoxyglucose to measure the local rates of glucose utilization within the brain has been applied to the binocular visual system of the Macaque monkey. This method, which pictorially displays the relative rates of glucose consumption in the component structures of the brain, delineates the regions of altered functional activity because of the close relationship between functional activity and energy metabolism. Bilateral retinal stimulation results in the delineation of different rates of glucose consumption in at least four cytoarchitectural layers of the striate cortex. The most intense metabolic activity appears to be in Layer IV, the locus of the termination of the geniculocortical pathway. Bilateral visual occlusion lowers the rates of glucoes consumption in striate cortex and markedly reduces the metabolic differentiation of the various layers. Unilateral visual deprivation delineates the laminae of the lateral geniculate body and the ocular dominance columns of the striate cortex. It also results in the autoradiographic visualization of regions with normally monocular input in the striate cortex, such as the rostral portions of the mushroom-like configurations in the calcarine cortex, which represent the extreme temporal crescents of the visual fields, and small regions in the most caudal part of the mushroom configurations, which are believed to represent the cortical loci of the blind spotsof the visual fields.

Animals↗
PubMed2007

Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism.

Albumin excretion marks early glomerular injury in hypertension. This study investigated heritability of albumin excretion in twin pairs and its genetic determination by adrenergic pathway polymorphism. Genetic associations used single nucleotide polymorphisms at adrenergic pathway loci spanning catecholamine biosynthesis, storage, catabolism, receptor action, and postreceptor signal transduction. We studied 134 single nucleotide polymorphisms at 46 loci for a total of >51,000 genotypes. Albumin excretion heritability was 45.2+/-7.4% (P=2x10(-7)), and the phenotype aggregated significantly with adrenergic, renal, metabolic, and hemodynamic traits. In the adrenergic system, excretions of both norepinephrine and epinephrine correlated with albumin. In the kidney, albumin excretion correlated with glomerular and tubular traits (Na(+) and K(+) excretion; fractional excretion of Na(+) and Li(+)). Albumin excretion shared genetic determination (genetic covariance) with epinephrine excretion, and environmental determination with glomerular filtration rate and electrolyte intake/excretion. Albumin excretion associated with polymorphisms at multiple points in the adrenergic pathway: catecholamine biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention, diagnosis, and treatment.

Adolescent↗