DDC
Aromatic-L-amino-acid decarboxylase (EC 4.1.1.28) (AADC) (DOPA decarboxylase) (DDC) [AADC]
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Sarcopenia is characterized by the loss of muscle mass and strength (muscle atrophy) because of aging or chronic diseases, such as chronic liver disease (CLD). Different mechanisms are involved in skeletal muscle atrophy, including decreased muscle fibre diameter and myosin heavy chain levels and increased ubiquitin-proteasome pathway activity, oxidative stress and myonuclear apoptosis. We recently found that all these mechanisms, except myonuclear apoptosis, which was not evaluated in the previous study, were involved in muscle atrophy associated with hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced CLD. In the present study, we evaluated the involvement of myonuclear apoptosis in CLD-associated sarcopenia and the effect of N-acetyl cysteine (NAC) treatment on muscle strength and apoptosis, using a DDC-supplemented diet-fed mouse model. Four-month-old male C57BL6 mice were fed with a standard or DDCsupplemented diet for six weeks in the absence or presence of NAC treatment. Our results showed that NAC attenuated the decrease in muscle fibre diameter and muscle strength associated with CLD-induced muscle wasting in gastrocnemius (GA) muscle of DDC-supplemented diet-fed mice. In addition, in GA muscle of the mice fed with DDC-supplemented diet-induced CLD showed increased myonuclear apoptosis compared with the GA muscle of the control diet-fed mice, as evidenced by increased apoptotic nuclei number, caspase-8 and caspase-9 expression, enzymatic activity of caspase-3 and BAX/BCL-2 ratio. NAC treatment inhibited all the mechanisms associated with myonuclear apoptosis in the GA muscle. To our knowledge, this is the first study which reports the redox regulation of muscle strength and myonuclear apoptosis in CLD-induced sarcopenia.
MeSH Terms
- Acetylcysteine
- Aging
- Animals
- Apoptosis
- Disease Models, Animal
- End Stage Liver Disease
- Humans
- Mice
- Muscle Fibers, Skeletal
- Muscular Atrophy
- Oxidative Stress
- Pyridines
- Sarcopenia
Keywords
- Sarcopenia
- UPP oxidative stress
- apoptosis
- chronic liver disease
- hepatotoxin.
Disorders of the biliary tree develop and progress differently according to patient age. It is currently not known whether the aging process affects the response to injury of cholangiocytes. The aim of this study was to identify molecular pathways associated with cholangiocyte aging and to determine their effects in the biological response to injury of biliary cells. A panel of microRNAs (miRs) involved in aging processes was evaluated in cholangiocytes of young and old mice (2 months and 22 months of age, respectively) and subjected to a model of sclerosing cholangitis. Intracellular pathways that are common to elevated miRs were identified by in silico analysis. Cell proliferation and senescence were evaluated in Twinfilin-1 (Twf1) knocked-down cells. In vivo, senescence-accelerated prone mice (Samp8, a model for accelerated aging), Twf1 , or their respective controls were subjected to DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine). Cholangiocytes from DDC-treated mice showed up-regulation of a panel of aging-related miRs. Twf1 was identified by in silico analysis as a common target of the up-regulated miRs. Twf1 expression was increased both in aged and diseased cholangiocytes, and in human cholangiopathies. Knock-down of Twf1 in cholangiocytes reduced cell proliferation. Senescence and senescence-associated secretory phenotype marker expression increased in Twf1 knocked-down cholangiocytes following pro-proliferative and pro-senescent (10-day lipopolysaccharide) stimulation. In vivo, Samp8 mice showed increased biliary proliferation, fibrosis, and Twf1 protein expression level, whereas Twf1 had a tendency toward lower biliary proliferation and fibrosis following DDC administration compared with control animals. Conclusion: We identified Twf1 as an important mediator of both cholangiocyte adaptation to aging processes and response to injury. Our data suggest that disease and aging might share common intracellular pathways.
MeSH Terms
- Aging
- Animals
- Biliary Tract
- Cell Proliferation
- Cells, Cultured
- Cellular Senescence
- Cholangitis, Sclerosing
- Disease Models, Animal
- Humans
- Mice
- MicroRNAs
- Microfilament Proteins
- Random Allocation
- Sensitivity and Specificity
This study was conducted to better understand the life history of Parthenolecanium corni (Bouché) and Parthenolecanium quercifex (Fitch) (Hemiptera: Coccidae), and to develop degree-day models for crawler emergence of the two soft scale species in Georgia, North Carolina, South Carolina, and Virginia. Both species were univoltine in the southeastern United States. In South Carolina, eggs hatched from mid-April to early June; second instars began to appear in September and migrated to twigs to overwinter in October; and third instars and adults appeared in mid-March to early April. Each parthenogenetic female produced on average 1,026 ± 52 eggs. Fecundity was positively correlated to the fresh weight, length, width, and height of gravid females. Gross reproductive rate (GRR) was 695.98 ± 79.34 ♀/♀, net reproductive rate (Rº) was 126.36 ± 19.03 ♀/♀, mean generation time (TG) was 52.61 ± 0.05 wk, intrinsic rate of increase (rm) was 0.04 ♀/♀/wk, and finite rate of increase (λ) was 1.04 times per week. Crawlers first occurred across Georgia, North Carolina, South Carolina, and Virginia in 2011-2013 when 524-596 Celsius-degree-days (DDC) had been accumulated with the single sine estimation method, or 411-479 DDC with the simple average method, at the base temperature of 12.8 °C and the start date of 1 January. These regional models accurately predicted the date of crawler emergence within 1 wk of the actual emergence in 2014.
MeSH Terms
- Animals
- Body Size
- Female
- Fertility
- Hemiptera
- Life History Traits
- Longevity
- Models, Biological
- Seasons
- Southeastern United States
- Species Specificity
Keywords
- degree-day model
- pest management
- shade tree
- soft scale
The ATBF1 gene encodes transcription factors containing four homeodomains and multiple zinc finger motifs. However, the gene products have yet to be identified and the role remains unknown in vivo. In this study, we raised an antiserum for ATBF1 and found high levels of expression of ATBF1 in developing rat brain. Western and Northern blot analyses detected a 400 kDa protein and 12.5 kb mRNA in developing rat brain, respectively; both corresponding to ATBF1-A but not the B isoform. The protein was highly expressed in the midbrain and diencephalon and mRNA was highly expressed in the brainstem, mostly in embryo and neonatal brain. Immunohistochemistry identified postmitotic neurons in the brainstem as the major site of ATBF1 expression, and the expression levels varied depending on age of and location in the brain. Expression was transient and weak in the precursor cells at early neurogenesis. ATBF1 decreased postnatally, but remained in mature neurons, including those expressing DOPA decarboxylase (DDC). High levels of ATBF1 were expressed in precursor cells in accordance with neurogenesis and were continued to the mature neurons in specific areas such as the inferior colliculus. Expression was not significant from precursor cells to mature neurons in the cerebral cortex and hippocampus. ATBF1 and its Drosophila homolog, Zfh-2, are known to regulate cell differentiation and proliferation via the interaction with either of the basic helix-loop-helix transcription factors, c-myb, or the DDC gene. Together with these reported functions the expression features detected here suggest that ATBF1 may participate in the regulation of neuronal cell maturation or region-specific central nervous system differentiation.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Brain
- Cell Differentiation
- Cell Division
- Dopa Decarboxylase
- Fetus
- Gene Expression Regulation, Developmental
- Helix-Loop-Helix Motifs
- Homeodomain Proteins
- Immunohistochemistry
- Neurons
- Protein Isoforms
- RNA, Messenger
- Rats
- Rats, Wistar
- Stem Cells
Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.
MeSH Terms
- Animals
- Base Sequence
- Chromosome Mapping
- DNA
- Dopa Decarboxylase
- Drosophila melanogaster
- Female
- Genes, Insect
- Genetic Complementation Test
- Genetic Variation
- Longevity
- Male
- Molecular Sequence Data
- Mutation
- Polymorphism, Genetic
- Quantitative Trait Loci
- Sequence Homology, Nucleic Acid
- Species Specificity
Maternal thyroid status influences early brain development and, consequently, cognitive and motor function in humans and rats. The biochemical targets of maternal thyroid hormone (TH) action in fetal brain remain poorly defined. A partially thyroidectomized rat dam model was therefore used to investigate the influence of maternal hypothyroxinemia on the specific activities of cholinergic and monoaminergic neurotransmitter metabolic enzymes in the developing brain. Maternal hypothyroxinemia was associated with reduced monoamine oxidase (MAO) activity in fetal whole brain at 16 and 19 days gestation (dg). A similar trend was observed for choline acetyltransferase (ChAT) activity. In contrast, DOPA decarboxylase (DDC) activity was markedly elevated at 21 dg. Further study of these enzymes at 14 dg showed no differences between normal and experimental progeny - suggesting they become TH sensitive after this age. Tyrosine hydroxylase (TyrH) and acetylcholinesterase (AChE) activities were unaffected prenatally. During postnatal development, the activities of TyrH, MAO, DDC and, to a lesser extent, AChE were increased in a brain region- and age-specific manner in experimental progeny. The prenatal disturbances noted in this study may have wide-ranging consequences since they occur when neurotransmitters have putative neurotropic roles in brain development. Furthermore, the chronic disturbances in enzyme activity observed during postnatal life may affect neurotransmission, thereby contributing to the behavioural dysfunction seen in adult progeny of hypothyroxinemic dams.
MeSH Terms
- Aging
- Animals
- Brain
- Choline O-Acetyltransferase
- Disease Models, Animal
- Dopa Decarboxylase
- Female
- Fetus
- Male
- Monoamine Oxidase
- Neurotransmitter Agents
- Pregnancy
- Pregnancy Complications
- Prenatal Exposure Delayed Effects
- Rats
- Rats, Sprague-Dawley
- Thyroxine
Recent positron emission tomography (PET) studies using 3,4-[18F]fluorodihydroxyphenylalanine ([18F]fluorodopa) have reported little or no decrement in dopaminergic function in human striatum (caudate and putamen) during aging. In contrast, previous postmortem studies have reported marked age-dependent decreases in the activity of dopa decarboxylase (DDC), a variable upon which the PET determinations depend. Using quantitative blot immunolabeling techniques, we measured DDC protein concentrations in postmortem striata of 28 neurologically normal subjects ranging in age from 17 to 103 years. We found a significant, albeit modest, age-dependent decrease in the concentration of DDC protein in caudate (r = -0.50, p < 0.05) but not in putamen (r = -0.16, p > 0.05), with mean values of the 87-year-old group being 27% (caudate) and 12% (putamen) lower than those of the 30-year-old group. The absence of a robust effect of aging upon striatal DDC protein is consistent with the [18F]fluorodopa-PET studies that report either no change or only a relatively small decrease in striatal 18F accumulation during aging. To the extent that aging is associated with a substantial loss of striatal dopaminergic nerve terminals, the present results also suggest that DDC protein synthesis may be upregulated in those dopaminergic neurons that survive the aging process and, therefore, that striatal [18F]fluorodopa uptake indices may provide an overestimate of the number of dopaminergic nerve terminals during physiological aging.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Corpus Striatum
- Dihydroxyphenylalanine
- Dopa Decarboxylase
- Dopamine
- Female
- Humans
- Male
- Middle Aged
- Tomography, Emission-Computed
Superior cervical ganglion (SCG) neurons taken from perinatal rats and dissociated in culture develop cholinergic properties. This report examines this "plasticity" of neurotransmitter function with regard to its dependence on the stage of neuronal development. Explants of SCG from rats ranging in age from 2 d to adult were cultured, and the number of neurons surviving after 6 wk in culture was evaluated. The activities of choline acetyltransferase (ChAc) and DOPA decarboxylase (DDC) were assayed for each age group over time in culture, and the cytochemistry of the synaptic vesicle population was studied after norepinephrine loading and KMnO4 fixation. The specific activity of ChAc in all explants fell during the first 3--4 d in culture (secondary to degeneration of presynaptic terminals), with an increase during the next 30 d in explants from all age groups except in those from the 22-d-old and adult rats. The highest activity found after 1 mo in culture was in explants from 2-d-old rats (62.5 mmol per kg dry wt per h); the lowest was in explants from adults (1.3 nmol per kg dry wt per h). After 1 mo in vitro, there were no significant differences in DDC activity among explants from animals of any age (similar to approximately 220 mmol per kg dry wt per h). Co-culture of the SCG explants with heart muscle increased even further the ChAc activity in explants from 2-d-old rats but not in explants from 16-d-old and 6.5-wk-old animals. The cytochemistry of the synaptic vesicle population in 1-mo-old cultures correlated well with the ChAc activity; when the ChAc activity was high, the proportion of synaptic vesicles with clear centers was 71--88%. In explants from adult animals, only 12% of the vesicles contained clear centers. From these data we conclude that the maturity of the SCG neuron influences the degree to which it is able to adjust its neurotransmitter mechanisms. That the axons of this neuron are interacting with target tissues during the time that neurotransmitter plasticity is retained suggests that interaction with the target may play a role in the determination of transmitter type.
MeSH Terms
- Aging
- Animals
- Choline O-Acetyltransferase
- Culture Techniques
- Dopa Decarboxylase
- Female
- Ganglia, Sympathetic
- Male
- Neurons
- Rats
- Synaptic Vesicles
Reports from several laboratories on a shorter life span of erythrocytes (E) in old animals and humans, induced the authors to search for a simple method for determining the younger age distribution of E in the blood of 20 old (over 70), as compared to 20 young (below 40), healthy donors. The following tests were performed: 1) Density Distribution of Cells (DDC), 2) Osmotic Fragility, 3) Agglutinability of E by Poly-L-lysine, 4) Analysis of Aspartate Amino Transferase (AST) activity, 5) Test for the presence of immunoglobulin on the surface of E (rosette formation on K562 cells); and 6) All the usual clinical and hematological tests were performed in order to avoid pathology. The most significant difference between the blood of the young and the old was found in the DDC. The shift of the cumulative curve indicated a younger population of cells in the blood of the elderly. The activity of AST was higher in the blood of the elderly, also indicating a younger cell population. The rosette formation was higher with the E from the blood of the elderly, indicating that the E, had more immunoglobulins on their surface than the E from the blood of the younger donors.
MeSH Terms
- Agglutination Tests
- Aging
- Antibodies
- Aspartate Aminotransferases
- Blood Donors
- Cell Membrane
- Cell Survival
- Erythrocyte Count
- Erythrocytes
- Humans
- Osmotic Fragility
- Polylysine
- Reference Values
The glutathione system (reduced and oxidized glutathione; redox index) was studied in the forebrain of male Wistar rats of 5, 15, and 25 months of age following the administration for 2 months in drinking water of chemicals that induce oxidative stress: paraquat and diethyldithiocarbamate (DDC) to increase superoxide radical formation, aminotriazole and hydrogen peroxide to increase hydroxyl radical generation, as well as diamide and ferrous chloride to decrease the glutathione cycle activity. Chronic oral administration of phosphatidylcholine for 2 months was evaluated in 25-month-old rats. Aging accentuated the changes produced by chemicals that induce oxidative stress; i.e., the changes in the glutathione redox index were most pronounced in the forebrains of the older paraquat-, DDC-, H2O2-, and diamide-treated rats. Markedly different adaptative changes occurred within the various drug groups. The reduced glutathione was increased (by paraquat, DDC and aminotrazole), decreased (by H2O2) or unchanged (by iron and diamide). Furthermore, in older rats, paraquat and DDC increased the glutathione redox index, whereas H2O2 and diamide decreased the glutathione redox index or were ineffective (i.e., aminotriazole, iron). The glutathione redox index altered by chronic drug administration was modified by the concomitant administration of phosphatidylcholine.
MeSH Terms
- Administration, Oral
- Aging
- Amitrole
- Animals
- Ditiocarb
- Frontal Lobe
- Glutathione
- Hydrogen Peroxide
- Male
- Oxidation-Reduction
- Oxygen
- Paraquat
- Phosphatidylcholines
- Rats
- Rats, Inbred Strains
- Superoxides
Because the gastrin molecule must be alpha-amidated to have maximum biological activity, rat pups from 1 to 6 wk of age were treated with dexamethasone (2 mg.kg-1.day-1) for 3 or 7 days, diethyldithiocarbamate (DDC; 400 mg.kg-1.day-1 x 3 days), dexamethasone and DDC, pentagastrin (750 micrograms.kg-1.day-1), or bombesin (40 micrograms.kg-1.day-1) for 3 days to determine the effects of these agents on alpha-amidation and gastrin and glycine extended gastrin (G-Gly) concentration in the stomach. Three day treatment with dexamethasone increased gastrin concentration by increasing amidation in pups before 5 wk of age and thereafter by enhancing preprogastrin synthesis or processing. Seven day dexamethasone treatment had no substantial effect on amidation. DDC universally inhibited amidation and affected a sustained increase in gastrin plus G-Gly concentration after the third week of life. Dexamethasone did not reverse the effects of DDC. Pentagastrin increased amidation in 1-, 3-, and 6-wk old rat pups but had no consistent effect on peptide concentration. Bombesin increased the sum of gastrin and G-Gly concentration in all but 1- and 5-wk old pups but had variable effects on alpha-amidation. We conclude that alterations in gastrin alpha-amidation have age-specific effects on tissue gastrin and G-Gly concentration and speculate that changes in tissue gastrin and G-Gly stores available for release might ultimately affect parietal cell and G-cell function during development.
MeSH Terms
- Aging
- Amides
- Animals
- Animals, Newborn
- Bombesin
- Dexamethasone
- Ditiocarb
- Gastric Mucosa
- Gastrins
- Pentagastrin
- Rats
- Rats, Inbred Strains
- Stomach