Papers by Diptendu Chatterjee
Journal of biochemical and molecular toxicology, 2003
Sulfur mustard has been used as a vesicant chemical warfare agent. To understand the mechanism by... more Sulfur mustard has been used as a vesicant chemical warfare agent. To understand the mechanism by which mustard gas exposure causes respiratory damage, we have used 2-chloroethyl ethyl sulfide (CEES) as a mustard analog. Our initial studies have shown that guinea pigs exposed to CEES intratracheally accumulate high levels of TNF-alpha. Accumulation of TNF-alpha leads to activation of both acid and neutral sphingomyelinases, resulting in high accumulation of ceramides, a second messenger involved in cell apoptosis. In addition, NF-kappa B was activated for a short period (1-2 h after exposure) as determined by mobility shift assay. Supershift assays indicated that both p50 and p65 of NF-kappa B were activated due to CEES exposure. However, NF-kappa B rapidly disappeared after 2 h. It is possible that the initial activation of NF-kappa B was an adaptive response to protect the cells from damage since NF-kappa B is known to inhibit TNF-alpha/ceramide-induced cell apoptosis. Since NF-ka...
Cellular and Molecular Neurobiology, 1992
No difference was observed in the in vitro growing ability of granule cells isolated from hypothy... more No difference was observed in the in vitro growing ability of granule cells isolated from hypothyroid or normal rat brain. When granule cells were taken from hypothyroid rat brain and grown in normal culture medium containing 10% fetal calf serum, they behaved similarly to the granule cells obtained from normal rat brain.
Science, 1991
... Further experiments, in young, senescent, and neoplastic cell lines are warranted for quantif... more ... Further experiments, in young, senescent, and neoplastic cell lines are warranted for quantifying the ratio of cdc25to weel expres-sion in subsequent ... MUNMUN CHAKRABORTY, DIPTENDU CHATTERJEE, SAKARI KELLOKUMPU, HOWARD RASMUSSEN, ROLAND BARON* ...
Proceedings of the National Academy of Sciences, 1994
Calcitonin (CT), which regulates serum calcium through its actions in bone and the kidney tubule,... more Calcitonin (CT), which regulates serum calcium through its actions in bone and the kidney tubule, also has a potent natriuretic effect in vivo. Na reabsorption in the proximal kidney tubule is mostly dependent on the activity of the Na,K-ATPase and the apical Na/H exchanger. We have previously shown that CT regulates the activity of the Na,K-ATPase in the proximal kidney tubule cell line LLC-PKj in a cell cycle-dependent manner. We report here that, in the same
Neurochemical Research, 1986
Plasma membranes from neuronal perikarya (N), protoplasmic astrocytes (A) and oligodendrocytes (O... more Plasma membranes from neuronal perikarya (N), protoplasmic astrocytes (A) and oligodendrocytes (O) of rat brains were analysed with respect to their protein and glycoprotein contents and specificities. SDS-polyacrylamide gel electrophoresis revealed a total number of 23, 17, and 17 major proteins in N, A, and O respectively. Periodate-Schiff's staining showed that approximately 40-60% of these proteins were glycoproteins. The reactivity of these glycoproteins to Con A and WGA was also studied. Selective iodination of whole cells followed by electrophoresis and autoradiography indicated that of the major proteins, only 25% of neuronal and 60% of astroglial and oligodendroglial membrane proteins were exposed outside the cell surface. The overall results suggest that membrane proteins of each of the three cell types studied here have characteristically different internal and external markers differing insize, glycoprotein content, and reactivity of the glycoproteins to lectins.
Journal of Biochemical and Molecular Toxicology, 2004
Mustard gas has been used as a vesicant chemical warfare agent. However, a suitable biomarker for... more Mustard gas has been used as a vesicant chemical warfare agent. However, a suitable biomarker for monitoring mustard gas exposure is not known. We observed that the hairs of the guinea pigs exposed intratracheally to subacute doses of 2-chloroethyl ethyl sulfide (CEES), a mustard analog, came out very easily though there was no sign of skin lesions or skin damage. Also the hairs looked rough and dry and lost the shiny glaze. There was no recovery from this hair loss, though the animals never became hairless, following CEES exposure. Hairs were observed in this study both visually and with light microscopy. Treatment with N-acetylcysteine (NAC) prior to CEES exposure could prevent the hair loss completely. Hence, sudden hair loss might be a good biomarker for subacute exposure of mustard gas to subjects at risks when the victims might have no other visible symptom of toxicity. C
Biochemistry, 1993
The osteoclast proton pump (OC H(+)-ATPase) differs from other vacuolar H(+)-ATPases (V-ATPases) ... more The osteoclast proton pump (OC H(+)-ATPase) differs from other vacuolar H(+)-ATPases (V-ATPases) in its sensitivity to vanadate and in the subunit composition of its catalytic domain, where isoforms of subunits A and B are expressed [Chatterjee et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 6257-6261]. In the present study, the sensitivity of the osteoclast H(+)-ATPase to various oxyanions was tested. The results indicate that H+ transport by microsomal preparations isolated from chicken osteoclasts is 20-100-fold more sensitive to nitrate that any other animal and fungal V-ATPases and 10-20-fold more sensitive than plant V-ATPases, as is the ATPase activity of the affinity-purified enzyme. This inhibition by nitrate is not due to a chaotropic effect of the oxyanion and is complete at 1 mM concentrations with an IC50 of 100 microM. In contrast, proton transport by the OC H(+)-ATPase was insensitive to other oxyanions (phosphate, sulfate, and acetate) which inhibit other V-ATPases. These results further demonstrate that the proton pump present in osteoclast membranes differs from other vacuolar ATPases. It is speculated that, since cells of the macrophage lineage can generate high intracellular concentrations of nitrate, it may be possible to physiologically or therapeutically regulate the activity of the OC H(+)-ATPase in the osteoclast without affecting the other V-ATPases in the same or in other cells.
Biochemical and Biophysical Research Communications, 2006
The full spectrum of physiological effects resulting from exposure to sulfur mustard and its anal... more The full spectrum of physiological effects resulting from exposure to sulfur mustard and its analogs is currently unknown. In a guinea pig model, initially selected to study the role of an inflammatory cytokine cascade in mustard gas induced lung injury, we observed significant body weight gain in guinea pigs exposed to an intratracheally injected single dose of 2-chloroethyl ethyl sulfide, a mustard analog. The body weight gain was not associated with any apparent change in appetite. To further elucidate a molecular basis for the observed weight gain, we evaluated candidate genes for the obese phenotype by quantitative RT-PCR. We observed a time-and dose-dependent decrease in guinea pig pro-opiomelanocortin (POMC) message following treatment with mustard gas. This reduction in POMC message is consistent with the onset of obesity in the animals. We hypothesize that the POMC melanocortin pathway provides a mechanistic basis for the observed effects of sulfur mustard on body weight.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1989
Partia~ purification of the dihydropyridine receptor from rat skeletal muscle demonstrated mainly... more Partia~ purification of the dihydropyridine receptor from rat skeletal muscle demonstrated mainly a 60 kDa band in SDS-polyacrylamide gel. An antibody raised against that protein behaved as a calcium channel agonist viz. Bay K8644. The affinity purified antibody, when added to cultured heart cells, increased the beat rate 40-80% depending on the titer of the antiserum. The antibody also woke up the beats of the cells previously blocked with the channel antagonist, nifedipine, lmmunoblot analysis indicated that the receptor of this antibody in heart cell membrane is also a 60 kDa protein.
Behavioural brain research, Jan 20, 2015
Stress is often considered an important factor in the development of alcohol addiction. In rodent... more Stress is often considered an important factor in the development of alcohol addiction. In rodents, various types of stressors have been shown to potentiate the effects of alcohol on behavioral responses, and to increase consumption of this substance. However, few have investigated the interaction between stress and alcohol in zebrafish. In the current study we present a repeated handling stress paradigm we developed for zebrafish, and examine whether stress alters alcohol induced behavioral and neurochemical responses. Our results show that repeated handling of zebrafish conducted for 2 consecutive days is sufficient to increase anxiety-like behavioral responses quantified 24hours post-stressor. Repeatedly handled zebrafish also exhibited a reduction in the levels of serotonin's metabolite, 5-hydroxyindole acetic acid (quantified by high precision liquid chromatography) compared to unhandled controls. A 60-minute acute exposure to 1% ethanol was found to significantly increase ...
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Variation among individuals may arise for several reasons, and may have diverse underlying mechan... more Variation among individuals may arise for several reasons, and may have diverse underlying mechanisms. Individual differences have been studied in a variety of species, but recently a new model organism has emerged in this field that offers both sophistication in phenotypical characterization and powerful mechanistic analysis. Recently, zebrafish, one of the favorites of geneticists, have been shown to exhibit consistent individual differences in baseline locomotor activity. In the current study, we further explore this finding and examine whether individual differences in locomotor activity correlate with anxiety-like behavioral measures and with levels of dopamine, serotonin and the metabolites of these neurotransmitters. In addition, we examine whether individual differences in locomotor activity are also associated with reactivity to the locomotor stimulant effects of and neurochemical responses to acute ethanol exposure (30 min long, 1% v/v ethanol bath application). Principal ...
Pharmacology, biochemistry, and behavior, 2015
Zebrafish have been successfully employed in the study of the behavioural and biological effects ... more Zebrafish have been successfully employed in the study of the behavioural and biological effects of ethanol. Like in mammals, low to moderate doses of ethanol induce motor hyperactivity in zebrafish, an effect that has been attributed to the activation of the dopaminergic system. Acute ethanol exposure increases dopamine (DA) in the zebrafish brain, and it has been suggested that tyrosine hydroxylase, the rate-limiting enzyme of DA synthesis, may be activated in response to ethanol via phosphorylation. The current study employed tetrahydropapaveroline (THP), a selective inhibitor of phosphorylated tyrosine hydroxylase, for the first time, in zebrafish. We treated zebrafish with a THP dose that did not alter baseline motor responses to examine whether it can attenuate or abolish the effects of acute exposure to alcohol (ethanol) on motor activity, on levels of DA, and on levels of dopamine's metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). We found that 60-minute exposure to 1%...
Zebrafish, Jan 22, 2015
Immediate early genes (IEGs) are transcription factors whose own transcription is initiated rapid... more Immediate early genes (IEGs) are transcription factors whose own transcription is initiated rapidly, for example, in the brain in response to environmental stimuli. c-fos is an IEG often used as a marker of neuronal activation. c-fos mRNA expression has started to be quantified and localized in the zebrafish brain following environmental manipulations but analysis of the expression of c-fos protein in the zebrafish brain has rarely been attempted. Here, we describe an immunofluorescence staining method for quantifying c-fos protein expression in different regions of the zebrafish brain. In addition, we expose zebrafish to caffeine, a positive control for c-fos activation in the brain. To confirm cell nucleus specific binding of the c-fos antibody, we counterstained brain sections with the nuclear fluorescent stain DAPI. Furthermore, we describe a method for reducing background autofluorescence often observed in zebrafish brain tissue. Our analysis showed that exposure to caffeine in...
Behavioural Brain Research, 2016
Zebrafish have become a popular animal model for behavioral neuroscience with an increasing numbe... more Zebrafish have become a popular animal model for behavioral neuroscience with an increasing number of studies examining the effects of pharmacological compounds targeting the brain. Exposure to MK-801, a non-competitive N-methyl-d-aspartate receptor antagonist has been shown to increase locomotor activity in zebrafish. However, others have failed to replicate this finding as several contradicting studies report no changes in locomotor activity following exposure to similar doses. In the current study we reconcile these behavioral reports by demonstrating that zebrafish do not exhibit changes in locomotor activity during exposure to non-sedative doses of MK-801. Interestingly, zebrafish do exhibit significant increases in locomotion if pre-treated with MK-801 followed by subsequent testing in a novel environment, which suggests the effects of MK-801 are context-dependent. In addition, we examine the potential role of the dopaminergic system in mediating MK-801's locomotor stimulant effect by quantifying the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the brains of zebrafish following a 30min exposure to 10μM of MK-801 (the dose found to induce the largest increase in locomotor activity). Our findings indicate that the MK-801-induced increase in locomotor activity is not accompanied by changes in whole-brain levels of dopamine or DOPAC. Overall, our results suggest that MK-801's context-dependent locomotor stimulant effect may be independent of whole-brain dopaminergic activation.
Behavioural brain research, Jan 25, 2015
The popularity of the zebrafish has been growing in behavioral brain research. Previously utilize... more The popularity of the zebrafish has been growing in behavioral brain research. Previously utilized mainly in developmental biology and genetics, the zebrafish has turned out to possess a complex behavioral repertoire. For example, it is a highly social species, and individuals form tight groups, a behavior called shoaling. Social isolation induced changes in brain function and behavior have been demonstrated in a variety of laboratory organisms. However, despite its highly social nature, the zebrafish has rarely been utilized in this research area. Here, we investigate the effects of chronic social isolation (lasting 90 days) on locomotor activity and anxiety-related behaviors in an open tank. We also examine the effect of chronic social isolation on levels of whole-brain serotonin and dopamine and their metabolites. We found that long-term social deprivation surprisingly decreased anxiety-related behavious during open-tank testing but had no effect on locomotor activity. We also fo...
Progress in neuro-psychopharmacology & biological psychiatry, Jan 2, 2015
Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral a... more Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantl...
Behavioural Brain Research, 2015
High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats incre... more High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6). All groups were fed a RV diet during lactation until weaning and a RV high fat (HF; 60% fat) diet for 16 weeks post-weaning. The HV, HVRF and HMethyl diet fed dams gained 45% more weight from 2 to 15 weeks post-weaning and their weight gain (WG) was positively associated with cumulative post-weaning food intake (FI). However, only HV dams had a reduced preference for a sucrose solution, lower mesolimbic dopamine (DA) turnover in the nucleus accumbens (NAc), and higher expression of several genes involved in FI regulation in the arcuate nucleus of the hypothalamus (ARC). Energy conserving peroxisome proliferator-activated receptor (Ppar)-γ in adipose and -α in liver was also greater in these dams consistent with their WG. In conclusion, HV, HVRF and HMethyl maternal diets exacerbate maternal WG when dams are exposed to a HF diet post-weaning. However, the diets differed in their effects on central and peripheral regulatory systems of energy balance.
Behavioral Neuroscience, 2014
Recent studies have started to examine the neurochemical and hormonal basis of behavior in zebraf... more Recent studies have started to examine the neurochemical and hormonal basis of behavior in zebrafish by examining biological correlates postmortem. However, it is unknown whether stress involved with experimental handling prior to euthanizing animals will have an impact on subsequent biological measures. In the current study, we expose zebrafish to a short net handling stressor (30 s) and examine the levels of monoamine neurotransmitters (dopamine, serotonin, and their metabolites) and whole-body cortisol at different intervals poststressor (0, 1, 5, 10, and 15 min). We report a time-dependent increase in the levels of cortisol, but no alterations in the levels of dopamine, DOPAC (dopamine's metabolite), serotonin, or 5HIAA (serotonin's metabolite) poststressor. The results demonstrate cortisol levels are more responsive to this type of stimulus compared with neurochemical measures.
Neurotoxicology and Teratology, 2014
Fetal Alcohol Spectrum Disorder (FASD) is a preventable disease of the child resulting from alcoh... more Fetal Alcohol Spectrum Disorder (FASD) is a preventable disease of the child resulting from alcohol (ethanol) consumption by pregnant women. Despite being preventable, FASD represents a prevalent problem throughout the world. Embryonic alcohol induced abnormalities in behavioral responses to social stimuli have been shown in humans and zebrafish. The neurobiological mechanisms underlying the abnormalities remain obscured. Here we start a mechanistic analysis by investigating the effect of embryonic alcohol exposure on the neurochemistry of zebrafish. The differing severity of symptoms seen in FASD may be partially due to genetic factors. To explore such genetic effects, here we analyzed two distinct zebrafish strains: AB and TU. Zebrafish were exposed to one of the following concentrations of alcohol, 0.00%, 0.25%, 0.50%, 0.75%, or 1.00% (vol/vol %) at 24 hours post-fertilization (hpf) for 2h. From whole brain extracts we analyzed the amount of neurotransmitters dopamine and serotonin and their metabolites across 4 different developmental time points: 15, 40, 70 and 102 days post-fertilization (dpf) using high performance liquid chromatography (HPLC). AB zebrafish exhibited a significant dose dependent embryonic alcohol exposure effect which increased in robustness with age. However, TU showed no such concentration effect: the levels of neurochemicals remained mainly unaltered by embryonic alcohol exposure in all age groups. We also analyzed the amount of alcohol reaching the embryo in the two strains and ruled out the possibility that TU has a more protective chorion. We conclude that the uncovered strain differences are due to genetic differences that protect TU from the deleterious effects of embryonic alcohol exposure.
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Papers by Diptendu Chatterjee