Adenosine Triphosphatase Activity Research Articles

Muscle fibre characteristics of a native pig breed longissimus lumborum muscle

The aim of this study was to investigate the histochemical parameters of muscle fibre in a Spanish autochthonous pig breed. Due to its fatty meat and high prolificacy, this pork is revered among local consumers. However, the aforementioned breed has become endangered. A total of 11 native pigs (Black Canary Pig) were evaluated. Longissimus lumborum muscle samples were collected in order to evaluate contractile and metabolic characteristics of the varying fibre types by histochemical staining techniques (nicotinamide adenine dinucleotide tetrazolium reductase [NADH-TR] and myosin adenosine triphosphatase activity [mATPase]). Cross-sectional area, diameter and percentage of the fibres were calculated. The oxidative fibre percentage was elevated (33.63%) which in turn can improve the colour, tenderness and juiciness of the meat, hence the glycolytic fibre percentage being moderate (66.37%). The size of three fibre types was higher than the values provided by other pig breeds. A higher percentage of IIB fibres is a disadvantage because these fibres cannot store a high percentage of intrafibrilar fat which could be linked to myopathic process. In conclusion, this autochthonous pig breed could potentially produce red meat and high quality, dry-cured pork products thanks to its remarkably high percentage of oxidative fibres, which naturally possess a greater capacity to store intramuscular fat.

Study on Hot Property of Aconiti Lateralis Radix Praeparata and Its Compatibility with Zingiberis Rhizoma Based on Animal Temperature Tropism

ObjectiveTo establish an objective method for evaluating the intrinsic characteristics between hot and cold properties of herbal drugs and to study the hot property of Aconiti Lateralis Radix Praeparata (ALRP) and its compatibility with Zingiberis Rhizoma (ZR) on animal temperature tropism. MethodsThe equipment with cold/hot pads was used to investigate the variety of temperature tropism among mice treated by ALRP and its compatibility with ZR. Meanwhile, the activities of adenosine triphosphatase (ATPase), total anti-oxidant capability (T-AOC), and total superoxide dismutase (T-SOD) were measured. ResultsCompared with the homologous ALRP group, the compatibility between ALRP and ZR (AZ) had a stronger action against the decreasing of remaining rate on hot pad (P < 0.05), suggesting an enhancement of cold tropism. Meanwhile, the internal indexes of Na+-K+-ATPase activity, Ca2+-Mg2+-ATPase activity, and oxygen consuming volume increased significantly (P < 0.05), suggesting an enhancement of energy metabolism. The changes of T-AOC and T-SOD activity suggested that AZ reinforced the anti-oxidative capability of mice. In addition, it could be inferred from cluster analysis that the activity of AZ was concretely stronger than that of homologous ALRP. ConclusionALRP and ZR are both herbs with hot property, but AZ has an enhanced trend of hot property. This external behavior of cold tropism and the internal activity of energy metabolism and anti-oxidant might reflect the internal hot property in an intuitive and objective way. The changes of ATPase activity of liver tissue might be the mechanism of drug action.

Modulation of crucial adenosinetriphosphatase activities due to U-74389G administration in a porcine model of intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) represents a partially-understood cerebrovascular disease of high incidence, morbidity and mortality. We, herein, report the findings of our study concerning the role of two important adenosinetriphosphatases (ATPases) in a porcine model of spontaneous ICH that we have recently developed (by following recent references as well as previously-established models and techniques), with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates that the examined ICH model does not cause a decrease in Na(+),K(+)-ATPase activity (the levels of which are responsible for a very large part of neuronal energy expenditure) in the perihematomal basal ganglia territory, nor a change in the activity of Mg(2+)-ATPase. This is the first report focusing on these crucial ATPases in the experimental setting of ICH and differs from the majority of the findings concerning the behavior of these (crucial for central nervous system cell survival) enzymes under stroke-related ischemic conditions. The administration of U-74389G (an established antioxidant) in this ICH model revealed an injury specific type of behavior, that could be considered as neuroprotective provided that one considers that Na(+),K(+)- and Mg(2+)-ATPase inhibition might in this case diminish the local ATP consumption.

Protective effect of ascorbic acid against ethanol-induced reproductive toxicity in male guinea pigs

The present study was undertaken to elucidate the effect of ascorbic acid on alcohol-induced reproductive toxicity and also to compare it with that of abstention. A total of thirty-six male guinea pigs were divided into two groups and were maintained for 90 d as control and ethanol-treated groups (4 g/kg body weight (b.wt.)). After 90 d, ethanol administration was stopped and animals in the control group were divided into two groups and then maintained for 30 d as the control and control+ascorbic acid groups and those in the ethanol-treated group as ethanol abstention and ethanol+ascorbic acid (25 mg/100 g b. wt.) groups. Animals treated with ethanol showed a significant decline in sperm quality (P<0·001), decreased activity of steroidogenic enzymes (P<0·05) and reduced serum testosterone (P<0·05), luteinising hormone and follicle-stimulating hormone levels, decrease in the activity of testicular succinate dehydrogenase, adenosine triphosphatase, sorbitol dehydrogenase and reduction in fructose content (P<0·05). It also caused an increase in testicular malondialdehyde levels (P<0·05) and decrease in the levels of glutathione content (P<0·001) of testes. Ascorbic acid levels in testes and plasma were also reduced (P<0·001) in ethanol-fed animals. Ascorbic acid supplementation altered all these parameters and produced a better and faster recovery from alcohol-induced reproductive toxicity than abstention. The mechanism of action of ascorbic acid may be by reducing the oxidative stress and improving antioxidant status, which eventually changed the microenvironment of testes and enhanced the energy needed for motility of sperms, improved the sperm morphology and elevated the testosterone and gonadotropin levels.

Mechanisms controlling vacuolar H+-adenosine triphosphatase activity: targets for the development of new therapeutic agents for the management of osteoporosis

Mechanisms controlling vacuolar H+-adenosine triphosphatase activity: targets for the development of new therapeutic agents for the management of osteoporosis L Shannon Holliday,1,2 Nancy Huynh,1 Jian Zuo,1 Edgardo J Toro1,31Department of Orthodontics, University of Florida College of Dentistry, Gainesville, FL, USA; 2Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL, USA; 3Department of Advanced Graduate Dental Education, University of Puerto Rico School of Dental Medicine, San Juan, Puerto RicoAbstract: Recent genetic studies show that mutations in vacuolar H+-adenosine triphosphatase (V-ATPase) subunit isoforms that are selectively expressed in osteoclasts (a3 and d2) lead to both reduced bone resorption and increased bone formation. This implies that pharmaceuticals targeting these subunits or activities that are linked to these subunits might prove to be bone anabolic. The fact that V-ATPase is a ubiquitous &quot;housekeeping&quot; enzyme has made it challenging to directly target the enzymatic activity of the subset of V-ATPases involved in bone resorption; however, the unique mechanisms that control the V-ATPases involved in bone resorption have begun to emerge. These include binding interactions with the cytoskeleton and with proteins involved in regulating the cytoskeleton and membrane trafficking, links to glycolysis, and surprising ties to the renin&ndash;angiotensin signaling network. Links between controlling mechanisms and subunit a3 have been identified, suggesting that it may be possible to develop agents that disrupt bone resorptive V-ATPase activity while leaving the housekeeping activities unhindered. The first steps toward using this new information to rationally design novel classes of therapeutic agents have been taken. Such agents might selectively act against osteoclasts both to prevent the initiation of osteoporosis and to restore already-compromised bone.Keywords: vacuolar H+-ATPase, enoxacin, luteolin, computational chemistry, microfilaments, ARF6

Jaggery Protects Hepatorenal Injury Induced by Acute Exposure to Carbon Tetrachloride in Wistar rats

In this study, we evaluated the protective activity of aqueous extract of jaggery against CCl4-induced hepatic-renal damage in rats. Jaggery was administered in one group at doses of 250, 500 and 750 mg/ kg body weight (bwt) (p.o., once only), and CCL4 was administered in another group at a dose of 1.5 ml/kg bwt (i.p., once only) to evaluate the protective effect of jaggery on induced oxidative damage in rats. Various blood and tissue biochemical studies were performed. The administration of toxicant significantly altered blood biochemical variables. Hepatic and renal lipid peroxidation (LPO) levels increased significantly, whereas considerable depletion was observed in reduced glutathione (GSH) level after intoxication. A remarkable decrease was observed in the activities of adenosine triphosphatase (ATPase) and glucose-6-phosphatase (G-6-Pase) after induction of toxicity. Treatment with extract at three different altered all measured biochemical variables, but greater hepatic-renal protection was observed at higher doses (750 mg/kg bwt) than at lower does (250 and 500 mg/kg bwt). Jaggery also reversed histopathological alterations. Thus, it may be concluded that jaggery can be used to reduce hepatic and renal damage and may serve as an alternative medicine in hepatic and renal etiology.

Effect of an antioxidant combination on the distribution of acetylcholinesterase and adenosine triphosphatase activities in the cerebellum of in lindane-intoxicated mice

Effect of an antioxidant combination on the distribution of acetylcholinesterase and adenosine triphosphatase activities in the cerebellum of in lindane-intoxicated mice

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer&amp;#39;s disease

BackgroundTo sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl3)-induced Alzheimer’s model.MethodsLiposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl3 (50 mg/kg/day).ResultsThe study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl3, with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethy-larginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na+/K+-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl3-treated animals; however, RLs succeeded in normalization of AChE and Na+/K+ ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl3-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl3-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain.ConclusionRLs could be a potential drug-delivery system for ameliorating Alzheimer’s disease.

НАРУШЕНИЯ ЭНЕРГЕТИЧЕСКОГО МЕТАБОЛИЗМА ВО ВНУТРЕННИХ ОРГАНАХ ПРИ ЧЕРЕПНО-МОЗГОВОЙ ТРАВМЕ НА ФОНЕ САХАРНОГО ДИАБЕТА

Traumatic cranial injury is one of the leading reasons in the statistics of mortality. Modern ideas about the pathogenesis of traumatic brain injury based on the allocation of primary and secondary factors of brain damage. One of the main causes of secondary brain injury is hypoxia – insufficient provision with oxygen. Changes in oxygen balance lead to activation of oxidative stress, disturbances of mitochondria membranes and their death, and progression of energy metabolism imbalance caused by trauma. Millions of people worldwide suffer from diabetes mellitus. One of the factors that influences the development of complications of diabetes, is an accumulation of highly toxic peroxide compounds that intensify the processes of destabilization of cell membranes. Further research of peculiarities of oxidative stress and energy metabolism imbalance in diabetes associated with trauma will provide the basis for therapeutic directions to increase treatment options and improve patient health and well-being.Therefore, the purpose of this work is to study the effect of traumatic cranial injury on the energy supplying processes in the liver and kidneys of rats with streptozotocin diabetes, as well as establishing a link between impaired mitochondrial oxidation and the intensity of oxidative stress.Hundred adult male Wistar rats, weighing 180-220 g, were used in this study. Rats were assigned to one of four groups: (1) control animals (n=10); (2) rats with diabetes (n=10); (3) rats with closed cranial trauma (n=40); (4) animals with cranial trauma on the diabetes background (n=40). To induce diabetes, streptozotocin (“Sigma-Aldrich”,USA) was dissolved in citrate buffer (pH 4.5) and a single intra-peritoneal injection (60 mg/kg) was given to each animal. The application of the cranial injury was done according to the method developed in our laboratory. The rats were sacrificed under thiopental sodium anesthesia by total bloodletting from the heart. The rats of groups 3 and 4 were euthanized 3 h, 24 h, 5, and 14 days after the onset of the injury. Blood of the experimental animals was analyzed for succinate dehydrogenase, cytochrome oxidase, proton adenosine triphosphatase activity, the concentration of adenosine triphosphate, diphosphate, and monophosphate. Additionally, we studied the products of protein and lipid peroxidation.Succinate dehydrogenase activity decreased 22,6% after 3 h, by 38,8% after 24 h, by 34,7% after 5 days, and by 22,2% after 14 days post-traumatically in diabetic rats. The most pronounced decrease in cytochrome oxidase activity in the liver was 26,3 and 40 % after 5 and 14 days after TBI, respectively. These changes were accompanied by an increase in the proton adenosine triphosphatase activity in the liver by 42,1, 53,5, 68,6, 63,3 % after 3 h, 1, 5 and 14 days after injury, compared to injured rats without diabetes. Statistically significant increase in the products of protein and lipid peroxidation after traumatic cranial injury in combination with diabetes mellitus towards non-diabetic injured rats was observed.It has been established that there are inhibition of the respiratory chain enzymes activity (succinate dehydrogenase and cytochrome oxidase), an increase in the proton adenosine triphosphatase activity and a decrease in the concentration of adenosine triphosphate in the liver and kidneys of experimental animals with cranial trauma and diabetes. The degree of mitochondrial oxidation impairment and adenosine triphosphate synthesis processes positively correlates with the intensity of oxidative stress in the liver and kidneys. In the event of traumatic cranial injury on the background of concomitant diabetes mellitus, indicators of the mitochondrial energy supplying oxidation, the level of macroergic compounds and the intensity of oxidative stress were significantly worse compared to analogical indicators in the normoglycemic injured animals.

Alteration in haematological and biochemical parameters of Catla catla exposed to sub-lethal concentration of cypermethrin

A 60-day experiment was carried out to study the effect of sub-lethal concentration of cypermethrin (1/10th of LC(50)) exposure on haematological and biochemical parameters of the Indian major carp, Catla catla fingerlings. Under exposure, the total erythrocyte count, total leucocyte count, haemoglobin content and haematocrit were decreased. All the studied serum parameters viz. total serum protein, albumin, globulin contents and albumin-globulin ratio were significantly decreased in cypermethrin-exposed fishes. A marked increase was recorded in alanine aminotransferase and aspartate aminotransferase activities in liver, whereas lactate dehydrogenase activity of muscle and acetylcholine esterase activity in brain were inhibited in cypermethrin-exposed fish. The membrane transport enzymes (total adenosine triphosphatase, sodium-potassium adenosine triphosphatase and magnesium adenosine triphosphatase) activities were decreased significantly in the gills of C. catla exposed to sub-lethal concentration of cypermethrin. The present study indicates that sub-lethal exposure of C. catla fingerlings to cypermethrin alters the haematological and biochemical parameters.

Oxidative stress in farmed minks with self-biting behavior

Abstract Self-biting behavior (SBB) is a serious behavioral disorder in farmed minks, but little is known about the biological basis of this disorder. The present study examined for the first time the hepatic and cerebral oxidative stress biomarker levels in SBB minks and compared them with those in normal ones to study the association of oxidative stress and SBB in minks. Calcium-activated adenosine triphosphatase (Ca 2 + ATPase) activities were also determined to investigate whether the Ca 2+ pump in brain is affected. Twenty male SBB minks and 20 male normal minks were chosen in December. The brain and liver of each mink were harvested immediately after slaughter to test oxidative stress biomarkers. All parameters were determined by using a spectrophotometer. Our findings were as follows: SBB minks produced more malondialdehyde with 51% increase in brain ( P P P P P P P P P P

Gestational doxorubicin alters fetal thyroid–brain axis

Administration of chemotherapy during pregnancy may represent a big risk factor for the developing brain, therefore we studied whether the transplacental transport of doxorubicin (DOX) may affect the development of neuroendocrine system. DOX (25mg/kg; 3 times interaperitoneally/week) was given to pregnant rats during whole gestation period. The disturbances in neuroendocrine functions were investigated at gestation day (GD) 15 and 20 by following the maternal and fetal thyroid hormone levels, fetal nucleotides (ATP, ADP, AMP) levels and adenosine triphosphatase (Na+, K+-ATPase, Ca2+-ATPase and Mg2+-ATPase) activities in two brain regions, cerebrum and cerebellum. In control group, the levels of maternal and fetal serum thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), and fetal serum growth hormone (GH) increased from days 15 to 20, whereas in the DOX group, a decrease in maternal and fetal T4, T3 and increase in TSH levels (hypothyroid status) were observed. Also, the levels of fetal GH decreased continuously from GD 15 to 20 with respect to control group. In cerebrum and cerebellum, the levels of fetal nucleotides and the activities of fetal ATPases in control group followed a synchronized course of development. The fetal hypothyroidism due to maternal administration of DOX decreased the levels of nucleotides, ATPases activities, and total adenylate, instead, the adenylate energy charge showed a trend to an increase in both brain regions at all ages tested. These alterations were dose- and age-dependent and this, in turn, may impair the nerve transmission. Finally, DOX may act as neuroendocrine disruptor causing hypothyroidism and fetal brain energetic dysfunction.

Dietary microbial levan ameliorates stress and augments immunity inCyprinus carpiofry (Linnaeus, 1758) exposed to sublethal toxicity of fipronil

A 45-day feeding trial was conducted to study the stress ameliorating and immunomodulatory role of microbial levan in Cyprinus carpio fry exposed to sublethal dose (1/10th LC50) of fipronil [(±)-5-amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromethylsulfinylpyrazole-3-carbonitrile]. Two hundred and twenty-five fry were randomly distributed in five treatments in triplicates. Four purified diets were prepared with graded levels of microbial levan. Five different treatment groups were levan control L0P0 (basalfeed + 0% levan without exposure to pesticide); pesticide control L0P1 (basalfeed + 0% levan with exposure to pesticide); L0.25P1 (basalfeed + 0.25% levan with exposure to pesticide); L0.50P1 (basalfeed + 0.50% levan with exposure to pesticide) and L0.75P1 (basalfeed + 0.75% levan with exposure to pesticide). Lactate dehydrogenase (LDH), malate dehydrogenase (MDH) and fructose-1,6-diphosphatase (FDPase) activites were significantly (P < 0.05) increased, whereas alkaline phosphatase (ALP), adenosine triphosphatase (ATPase) and acetyl choline esterase (AchE) activities were significantly (P < 0.05) reduced in higher levan-fed groups. RBC, haemoglobin and WBC counts were significantly (P < 0.05) increased in the levan-fed groups. Similar trends were also observed for the total serum protein, globulin, NBT and lysozyme activities. Blood glucose and serum cortisol exhibited a third order polynomial relationship with increasing level of dietary levan. Overall result showed stress ameliorating, immunostimulating and protective role of microbial levan against fipronil-induced stress in C. carpio fry at 0.75% level of dietary levan supplementation.

Kinesin family member 14 is a candidate prognostic marker for outcome of glioma patients

Background & aim: Human kinesin superfamily proteins (KIFs) are a conserved class of microtubule-dependent molecular motor proteins with adenosine triphosphatase activity and motion characteristics. As a member of KIFs, KIF14 plays an important role in the regulation of cell cycle and mitotic progression. Deregulation of KIF14 has been found in several human malignancies and also has been demonstrated to be involved in tumor progression and related to patient survival. The aim of this study was to investigate the clinicopathological significance of KIF14 expression in glioma. Methods: Real-time quantitative RT-PCR assay was performed to detect KIF14 mRNA expression, and Western blot and immunohistochemistry analyses were performed to detect KIF14 protein expression in human gliomas and non-neoplastic brain tissues, respectively. Then, the association of KIF14 immunostaining with clinicopathological factors and prognosis of glioma patients was also statistically analyzed. Results: KIF14 mRNA and protein expression were respectively increased 5.5- and 4.2-fold on average in glioma tissues relative to non-neoplastic brain tissues (both P<0.001). Additionally, both KIF14 mRNA and protein expression increased with ascending pathological grade. Then, the high KIF14 immunostaining in glioma tissues was significantly associated with advanced pathological grade (P=0.008), low Karnofsky performance score (KPS) (P=0.02), high mitotic index (P=0.005) and Ki-67 index (P=0.008). Furthermore, both univariate and multivariate Cox regression analyses determined that KIF14 overexpression effectively predicted decreased overall survival in patients with gliomas. Conclusions: These findings offer the first convinced evidence that KIF14 expression in gliomas is tumor-specific and increased in more aggressive tumors. KIF14 might function as a candidate prognostic marker for human gliomas.

Atherosclerosis and atherosensitivity in two southwest Algerian desert rodents, Psammomys obesus and Gerbillus gerbillus, and in Rattus norvegicus.

Cardiovascular disease, including atherosclerosis, is the leading cause of death in patients with diabetes worldwide; thus, it is a major medical concern. The endothelium contributes to the control of many vascular functions, and clinical observations show that it is a primary target for diabetic syndrome. To get better insight into the mechanisms underlying atherosclerosis, we studied the interspecific differences in the arterial metabolisms of two, Psammomys obesus and Gerbillus gerbillus, as well as Rattus norvegicus (Wistar rat), well known for its atheroresistance. Twenty-two enzymatic activities and six macromolecular substances were histochemically compared in the two desert species and in Wistar aortas (abdominal and thoracic) and arteries (femoral and caudal) embedded in a common block. In the healthy adult rodents, enzyme activities were very intense. They demonstrated that aortic myocytes are capable of various synthesis and catabolism processes. However, considering the frequency of atherosclerosis and its phenotypes, significant differences appeared between the species studied. Our comparative study shows that aortic atherosensitive animals have several common metabolic characteristics, which are found in Psammomys rich in metachromatic glycosaminoglycans (involved in the inhibition of lipolysis and in calcification of the organic matrix), reduced activity in enzymes related to the Krebs cycle (weakening energetic power), and low lipolytic enzyme, adenosine triphosphatase, and adenosine diphosphatase activities. However, the most fundamental pathophysiological difference is the low lipolytic power of the aorta of Psammomys when compared to Wistar rats. This characteristic determines its atherosensitivity and makes this animal model more applicable to the experimental development of atherosclerosis.

Estrogenic compounds decrease growth hormone receptor abundance and alter osmoregulation in Atlantic salmon

Exposure of Atlantic salmon smolts to estrogenic compounds is shown to compromise several aspects of smolt development. We sought to determine the underlying endocrine mechanisms of estrogen impacts on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. Smolts in freshwater (FW) were either injected 3 times over 10days with 2μgg−1 17β-estradiol (E2) or 150μgg−1 4-nonylphenol (NP). Seawater (SW)-acclimated fish received intraperitoneal implants of 30μgg−1 E2 over two weeks. Treatment with these estrogenic compounds increased hepatosomatic index and total plasma calcium. E2 and NP reduced maximum growth hormone binding by 30–60% in hepatic and branchial membranes in FW and SW, but did not alter the dissociation constant. E2 and NP treatment decreased plasma levels of IGF-I levels in both FW and SW. In FW E2 and NP decreased plasma GH whereas in SW plasma GH increased after E2 treatment. Compared to controls, plasma chloride concentrations of E2-treated fish were decreased 5.5mM in FW and increased 10.5mM in SW. There was no effect of NP or E2 on gill sodium–potassium adenosine triphosphatase (Na+/K+-ATPase) activity in FW smolts, whereas E2 treatment in SW reduced gill Na+/K+-ATPase activity and altered the number and size of ionocytes. Our data indicate that E2 downregulates the GH/IGF-I-axis and SW tolerance which may be part of its normal function for reproduction and movement into FW. We conclude that the mechanism of endocrine disruption of smolt development by NP is in part through alteration of the GH/IGF-I axis via reduced GH receptor abundance.

Two ATPases

In this article, I reflect on research on two ATPases. The first is F(1)F(0)-ATPase, also known as ATP synthase. It is the terminal enzyme in oxidative phosphorylation and famous as a nanomotor. Early work on mitochondrial enzyme involved purification in large amount, followed by deduction of subunit composition and stoichiometry and determination of molecular sizes of holoenzyme and individual subunits. Later work on Escherichia coli enzyme utilized mutagenesis and optical probes to reveal the molecular mechanism of ATP hydrolysis and detailed facets of catalysis. The second ATPase is P-glycoprotein, which confers multidrug resistance, notably to anticancer drugs, in mammalian cells. Purification of the protein in large quantity allowed detailed characterization of catalysis, formulation of an alternating sites mechanism, and recently, advances in structural characterization.

Saccharomyces cerevisiae Dmc1 and Rad51 Proteins Preferentially Function with Tid1 and Rad54 Proteins, Respectively, to Promote DNA Strand Invasion during Genetic Recombination

The Saccharomyces cerevisiae Dmc1 and Tid1 proteins are required for the pairing of homologous chromosomes during meiotic recombination. This pairing is the precursor to the formation of crossovers between homologs, an event that is necessary for the accurate segregation of chromosomes. Failure to form crossovers can have serious consequences and may lead to chromosomal imbalance. Dmc1, a meiosis-specific paralog of Rad51, mediates the pairing of homologous chromosomes. Tid1, a Rad54 paralog, although not meiosis-specific, interacts with Dmc1 and promotes crossover formation between homologs. In this study, we show that purified Dmc1 and Tid1 interact physically and functionally. Dmc1 forms stable nucleoprotein filaments that can mediate DNA strand invasion. Tid1 stimulates Dmc1-mediated formation of joint molecules. Under conditions optimal for Dmc1 reactions, Rad51 is specifically stimulated by Rad54, establishing that Dmc1-Tid1 and Rad51-Rad54 function as specific pairs. Physical interaction studies show that specificity in function is not dictated by direct interactions between the proteins. Our data are consistent with the hypothesis that Rad51-Rad54 function together to promote intersister DNA strand exchange, whereas Dmc1-Tid1 tilt the bias toward interhomolog DNA strand exchange.

Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation

Cockayne syndrome (CS) is a rare human disorder characterized by pathologies of premature aging, neurological abnormalities, sensorineural hearing loss and cachectic dwarfism. With recent data identifying CS proteins as physical components of mitochondria, we sought to identify protein partners and roles for Cockayne syndrome group B (CSB) protein in this organelle. CSB was found to physically interact with and modulate the DNA-binding activity of the major mitochondrial nucleoid, DNA replication and transcription protein TFAM. Components of the mitochondrial transcription apparatus (mitochondrial RNA polymerase, transcription factor 2B and TFAM) all functionally interacted with CSB and stimulated its double-stranded DNA-dependent adenosine triphosphatase activity. Moreover, we found that patient-derived CSB-deficient cells exhibited a defect in efficient mitochondrial transcript production and that CSB specifically promoted elongation by the mitochondrial RNA polymerase in vitro. These observations provide strong evidence for the importance of CSB in maintaining mitochondrial function and argue that the pathologies associated with CS are in part, a direct result of the roles that CSB plays in mitochondria.

Dietary calcium induced cytological and biochemical changes in thyroid

Certain epidemiological studies revealed correlation between hard water consumption (with high calcium) and thyroid size of the population, though the possible alterations in thyroid physiology upon calcium exposure are still inconclusive. Adult male Wistar strain rats were subjected to calcium treatment at the doses of 0.5g%, 1.0g% and 1.5g% calcium chloride (CaCl2) for 60 days. The parameters studied were – thyroid gland weight, histopathology, histomorphometry; thyroid peroxidase (TPO), 5′-deiodinase I (DI), sodium–potassium adenosine triphosphatase (Na+–K+-ATPase) activities; serum total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), thyroid stimulating hormone (TSH) levels. Enlargement of thyroid with hypertrophic and hyperplastic changes, retarded TPO and 5′-DI but enhanced Na+–K+-ATPase activities, augmented serum total and free T4 and TSH but decreased total and free T3 levels and low T3/T4 ratio (T3:T4) were observed in the treated groups. All these findings indicate development of goitrogenesis upon exposure to excessive dietary calcium.