Ansuman Chattopadhyay - Academia.edu (original) (raw)

Papers by Ansuman Chattopadhyay

Proceedings of the National Academy of Sciences of the United States of America, 1999

The nonreceptor tyrosine kinase FAK ("focal adhesion kinase") is a key mediator of integrin signa... more The nonreceptor tyrosine kinase FAK ("focal adhesion kinase") is a key mediator of integrin signaling events controlling cellular responses to the extracellular matrix, including spreading, migration, proliferation, and survival. Integrin-ligand interactions stimulate FAK tyrosine phosphorylation and activation of FAK signaling functions. Here evidence is presented that the FAK autophosphorylation site Tyr-397 mediates a direct interaction with the C-terminal Src homology 2 domain of phospholipase C (PLC)-γ 1 and that this is required for both adhesion-dependent association of the two molecules and increased inositol phosphate production in mouse embryo fibroblasts. Overexpression of FAK and PLC-γ 1 in COS-7 cells increases PLC-γ 1 enzymatic activity and tyrosine phosphorylation, also dependent on FAK Tyr-397. However, FAK appears incapable of directly phosphorylating PLC-γ 1. These observations suggest a role for FAK in recruiting PLC-γ 1 to the plasma membrane at sites of cell-matrix adhesion and there promoting its enzymatic activity, possibly by releasing the repression caused by intramolecular interactions of the PLC-γ 1 Src homology domains and/or by positioning it for phosphorylation by associated Src-family kinases. These findings expand the known signaling functions of FAK and provide mechanistic insight into integrin-stimulation of PLC-γ 1.

International journal of oncology, 2009

Hypoxia and hypoxia inducible factor-1alpha (HIF-1alpha) play a critical role in glioblastoma (GB... more Hypoxia and hypoxia inducible factor-1alpha (HIF-1alpha) play a critical role in glioblastoma (GBM) which is characterized by highly aggressive and widespread cell invasion into adjacent normal brain tissue. The purpose of this study was to investigate the effect of the novel aminothiazole com-pound SNS-032 in glioblastoma cell invasion under hypoxic condition. SNS-032 is a potent and selective inhibitor of cyclin-dependent kinases 2, 7 and 9 and inhibits both cell cycle and transcription. We analyzed the effect of SNS-032 (0.5 microM) on HIF-1alpha expression and its major trans-regulating factors including COX-2, VEGF, MMP-2 and uPAR that are involved in cellular invasion in tumor hypoxia. Our observations demonstrate SNS-032: i) inhibited hypoxia-induced U87MG cell invasion and among all the other inhibitors tested, SNS-032 is the most effective, ii) blocked HIF-1alpha mediated transcription of COX-2, MMP-2, VEGF and uPAR expression in U87MG cells in response to hypoxia, iii) blo...

Mutation research, 1995

Based on their ability to induce sister-chromatid exchanges (SCEs) it is evident that thiol-conta... more Based on their ability to induce sister-chromatid exchanges (SCEs) it is evident that thiol-containing radioprotectors can induce DNA damage. However, there were contradictory findings when reduced glutathione (GSH) was tested using two cell lines. The present study demonstrated that GSH can induce SCEs and also delay in cell proliferation in mouse bone marrow cells in vivo. The presence of catalase significantly reduced GSH-induced SCE frequency down to catalase alone levels. An attempt was made to evaluate the effect of GSH treatment in buthionine sulfoximine (BSO)-treated mice (GSH-depleted mice) and the data indicate that induction of SCEs takes place without inducing a delay in cell proliferation or the generation of hydrogen peroxide. Probably, some unknown route is involved by which GSH-degraded product(s) induce SCEs in BSO-treated mice. Therefore, the induction of SCEs by GSH in normal mice may be largely due to hydrogen peroxide generation; however, the involvement of the ...

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences, 2013

Academy of Sciences, India. This e-offprint is for personal use only and shall not be selfarchive... more Academy of Sciences, India. This e-offprint is for personal use only and shall not be selfarchived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".

To bridge,the gap,between,the rising information needs,of biological,and,medical,researchers,and ... more To bridge,the gap,between,the rising information needs,of biological,and,medical,researchers,and the,rapidly,growing,number,of,online,bioinfor- matics resources, we have created the Online Bioinformatics,Resources,Collection (OBRC) at the Health,Sciences,Library,System,(HSLS) at,the University of Pittsburgh. The OBRC, containing 1542 major,online,bioinformatics,databases,and software tools, was constructed using the HSLS content,management,system,built on,the,Zope, , which automatically organizes the search,results,into categories,created,dynami- cally,based,on,the,textual,information,of,the retrieved,records. As the largest,online,collection of its kind,and,the only,one,with advanced,search results clustering, OBRC is aimed at becoming a one-stop,guided,information,gateway,to the major bioinformatics,databases,and,software,tools,on the,Web. OBRC is available,at the,University,of Pittsburgh’s,HSLS Web,site (http://www.hsls.pitt. edu/guides/genetics/obrc).

Proceedings of the National Academy of Sciences, 1999

The nonreceptor tyrosine kinase FAK (''focal adhesion kinase'') is a key mediator of integrin sig... more The nonreceptor tyrosine kinase FAK (''focal adhesion kinase'') is a key mediator of integrin signaling events controlling cellular responses to the extracellular matrix, including spreading, migration, proliferation, and survival. Integrin-ligand interactions stimulate FAK tyrosine phosphorylation and activation of FAK signaling functions. Here evidence is presented that the FAK autophosphorylation site Tyr-397 mediates a direct interaction with the C-terminal Src homology 2 domain of phospholipase C (PLC)-␥1 and that this is required for both adhesion-dependent association of the two molecules and increased inositol phosphate production in mouse embryo fibroblasts. Overexpression of FAK and PLC-␥1 in COS-7 cells increases PLC-␥1 enzymatic activity and tyrosine phosphorylation, also dependent on FAK Tyr-397. However, FAK appears incapable of directly phosphorylating PLC-␥1. These observations suggest a role for FAK in recruiting PLC-␥1 to the plasma membrane at sites of cellmatrix adhesion and there promoting its enzymatic activity, possibly by releasing the repression caused by intramolecular interactions of the PLC-␥1 Src homology domains and͞or by positioning it for phosphorylation by associated Src-family kinases. These findings expand the known signaling functions of FAK and provide mechanistic insight into integrinstimulation of PLC-␥1.

Molecular and Cellular Biology, 2009

Kinetoplastid flagellates attach a 39-nucleotide spliced leader (SL) upstream of protein-coding r... more Kinetoplastid flagellates attach a 39-nucleotide spliced leader (SL) upstream of protein-coding regions in polycistronic RNA precursors through trans splicing. SL modifications include cap 2-O-ribose methylation of the first four nucleotides and pseudouridine () formation at uracil 28. In Trypanosoma brucei, TbMTr1 performs 2-O-ribose methylation of the first transcribed nucleotide, or cap 1. We report the characterization of an SL RNA processing complex with TbMTr1 and the SLA1 H/ACA small nucleolar ribonucleoprotein (snoRNP) particle that guides SL 28 formation. TbMTr1 is in a high-molecular-weight complex containing the four conserved core proteins of H/ACA snoRNPs, a kinetoplastid-specific protein designated methyltransferase-associated protein (TbMTAP), and the SLA1 snoRNA. TbMTAP-null lines are viable but have decreased SL RNA processing efficiency in cap methylation, 3-end maturation, and 28 formation. TbMTAP is required for association between TbMTr1 and the SLA1 snoRNP but does not affect U1 small nuclear RNA methylation.

Journal of Biological Chemistry, 1999

The two SH2 (Src homology domain 2) domains present in phospholipase C-gamma1 (PLC-gamma1) were a... more The two SH2 (Src homology domain 2) domains present in phospholipase C-gamma1 (PLC-gamma1) were assayed for their capacities to recognize the five autophosphorylation sites in the epidermal growth factor receptor. Plasmon resonance and immunological techniques were employed to measure interactions between SH2 fusion proteins and phosphotyrosine-containing peptides. The N-SH2 domain recognized peptides in the order of pY1173 > pY992 > pY1068 > pY1148 > pY1086, while the C-SH2 domain recognized peptides in the order of pY992 > pY1068 > pY1148 > pY1086 and pY1173. The major autophosphorylation site, pY1173, was recognized only by the N-SH2 domain. Contributions of the N-SH2 and C-SH2 domains to the association of the intact PLC-gamma1 molecule with the activated epidermal growth factor (EGF) receptor were assessed in vivo. Loss of function mutants of each SH2 domain were produced in a full-length epitope-tagged PLC-gamma1. After expression of the mutants, cells were treated with EGF and association of exogenous PLC-gamma1 with EGF receptors was measured. In this context the N-SH2 is the primary contributor to PLC-gamma1 association with the EGF receptor. The combined results suggest an association mechanism involving the N-SH2 domain and the pY1173 autophosphorylation site as a primary event and the C-SH2 domain and the pY992 autophosphorylation site as a secondary event.

Developmental Biology, 2001

Release of Ca(2+) from intracellular stores at fertilization of mammalian eggs is mediated by ino... more Release of Ca(2+) from intracellular stores at fertilization of mammalian eggs is mediated by inositol 1,4,5-trisphosphate (IP3), but the mechanism by which the sperm initiates IP3 production is not yet understood. We tested the hypothesis that phospholipase C (PLC) activity introduced into the mouse egg as a consequence of sperm-egg fusion is responsible for causing Ca(2+) release. We demonstrated that microinjecting purified, recombinant PLCgamma1 protein into mouse eggs caused Ca(2+) oscillations like those seen at fertilization. However, the PLC activity in the minimum amount of purified PLCgamma1 protein needed to elicit Ca(2+) release when injected into eggs was approximately 500-900 times the PLC activity contained in a single sperm. This indicates that a single mouse sperm does not contain enough PLC activity to be responsible for causing Ca(2+) release at fertilization. We also examined whether phosphatidylinositol 3-kinase (PI3K) could have a role in this process, and found that several inhibitors of PI3K-mediated signaling had no effect on Ca(2+) release at fertilization.

Acta Oceanologica Sinica, 2012

Http Dx Doi Org 10 1080 02772248 2013 862392, Dec 19, 2013

Journal of Fluorescence, 2015

Fluorescence recognition of Zn(2+) in 100 % aqueous medium using 2-((1, 3 dihydroxy-2-(hydroxymet... more Fluorescence recognition of Zn(2+) in 100 % aqueous medium using 2-((1, 3 dihydroxy-2-(hydroxymethyl)propan-2 ylimino) methyl) phenol (SALTM) as ratiometric probe is reported. Moreover, SALTM can discriminate Zn(2+) from Cd(2+) very effectively. The binding constant and detection limit of the probe for Zn(2+) is 2.2 × 10(4) M(-1/2) and 2.79 × 10(-8) M respectively. Interestingly, corresponding naphthalene derivative (HNTM) having less water solubility fails to be a ratiometric sensor. SALTM can detect intracellular Zn(2+) in HeLa cervical cancer cells under fluorescence microscope. Moreover, DFT and TD-DFT studies support experimental findings.

Fluoride

: In an in vivo genotoxicity investigation of the action of fluoride (F) on bone marrow cells, so... more : In an in vivo genotoxicity investigation of the action of fluoride (F) on bone marrow cells, sodium fluoride (NaF) was administered through the drinking water of 2–3 month old Swiss albino mice for 30 days at lower (7.5, 15, and 30 mg/L) and higher concentrations (100 and 150 mg/L). Mitotic inhibition, chromosomal aberrations, and chromatid breaks were most pronounced in mice that received the relatively low dose of 15 mg NaF/L. The effects became obvious after the first week of treatment and were maximal after 3 months of sustained exposure. Chromosome aberrations induced by one month treatment with 15 mg NaF/L was significantly higher than those found with the 100 and 150 mg NaF/L concentrations. The total number of femur bone marrow cells remained unchanged in all the treatment groups except in the 150 mg NaF/L group, in which it declined significantly. F treatment did not elicit any change in the percentage of viable cells in the bone marrow. Depletion of S-phase fraction of b...

Vinylﬂuoride (VF) wasﬁrst synthesized by Frederic Swarts, a Belgian chemist in 1901, by the react... more Vinylﬂuoride (VF) wasﬁrst synthesized by Frederic Swarts, a Belgian chemist in 1901, by the reaction between zinc and 1,1-diﬂuoro-2-bromoethane. Modern preparation involves the reaction of acetylene and hydrogenﬂuoride (HF) in the presence of a mercury- or aluminum-based catalyst. The US Environmental Protection Agency (EPA) listed VF as a highproduction-volume chemical in 1990. According to National Toxicology Program (NTP), 2005, the annual production of VF in the United States was above 1 million pounds (454 000 kg) in 1990 and approximately 3.3 million pounds (1.5 million kg) in 2001.

Fluoride

: Administration of sodium fluoride (NaF) in lower (15 mg/L) and higher (150 mg/L) doses through ... more : Administration of sodium fluoride (NaF) in lower (15 mg/L) and higher (150 mg/L) doses through drinking water for 30 or 90 days in Swiss albino mice resulted in a decrease in the organo-somatic index (OSI) accompanied by a decline in the white pulp content of the spleen. The percentage of dead cells and decrease in white pulp content in the spleen were highest in mice exposed to the lower dose of fluoride (F) for 90 days. An elevated level of G 0 /G 1 fraction of cells was noticed in mice exposed to the higher dose of F for 30 days as well as to the lower dose of F for 90 days, suggesting a G 0 /G 1 blockage due either to inhibition of DNA synthesis or perturbation of synthesis of cyclin, a regulator of cell cycle. No trace of DNA damage was evident from the DNA fragmentation study in any treatment group.

Fluoride

: In vivo clastogenic effects of mitomycin-C (MMC) in bone marrow cells of four groups of young m... more : In vivo clastogenic effects of mitomycin-C (MMC) in bone marrow cells of four groups of young male Swiss albino mice exposed to 0, 7.5, 15, and 30 mg NaF/L in their drinking water for 30 days were investigated. The percentages of aberrant metaphases and chromosome aberrations in all F-treated mice were significantly increased. In another experiment, NaF pretreatment was followed by intraperitoneal administration of 4 mg MMC/kg bw. Results indicated that the two chemicals did not have a synergistic effect; instead, a notable suppression of the clastogenic effect of MMC occurred. As expected, mitotic indices (MI) in the bone marrow cells of the MMC-treated mice were significantly lower than in the controls. However, in the mice pretreated with 30 mg NaF/L, the percent of MI was greater than in the MMC-treated group without NaF exposure. Moreover, the percentages of aberrant metaphases and chromatid breaks were significantly higher in all the F groups than in the controls. NaF exposu...

Environmental Toxicology and Pharmacology, 2015

Sodium fluoride (NaF), used as pesticides and for industrial purposes are deposited in the water ... more Sodium fluoride (NaF), used as pesticides and for industrial purposes are deposited in the water bodies and therefore affects its biota. Zebrafish exposed to NaF in laboratory condition showed hyperactivity and frequent surfacing activity, somersaulting and vertical swimming pattern as compared to the control group. Reactive oxygen species level was elevated and glutathione level was depleted along with increased malondialdehyde content in the brain. Levels of glutathione-s-transferase (GST), catalase (CAT) and superoxide dismutase were also elevated in the treatment groups. Expression of mRNA of nuclear factor erythroid 2 related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein 1 (Keap1) during stress condition were observed along with Gst, Cat, NADPH: quinone oxidoreductase 1(Nqo1) and p38. Except Keap1, all other genes exhibited elevated expression. Nrf2/Keap1 proteins had similar expression pattern as their corresponding mRNA. The findings in this study might help to understand the molecular mechanism of fluoride induced neurotoxicity in fish.

Inorganica Chimica Acta, 2015

ABSTRACT Condensation of rhodamine B hydrazide with 4-formylbenzonitrile generates a Pd2+ selecti... more ABSTRACT Condensation of rhodamine B hydrazide with 4-formylbenzonitrile generates a Pd2+ selective probe (RDHDNB) that allows its naked eye and fluorescence recognition. Moreover, RDHDNB is useful to detect Pd2+ in human breast cancer cells MCF7, under normal and fluorescence microscope.

Toxicology mechanisms and methods, Jan 23, 2015

Generation of reactive oxygen species is one of the major contributors in arsenic-induced genotox... more Generation of reactive oxygen species is one of the major contributors in arsenic-induced genotoxicity where reduced glutathione (GSH) could be an important determining factor. To understand the role of endogenous GSH, arsenic trioxide (As2O3) was administered in buthionine sulfoximine (BSO)- and N-acetyl-l-cysteine (NAC)-treated mice. As2O3-induced significant chromosome aberrations (CAs) in all treatment groups compared with the control. BSO-treated mouse bone marrow cells showed significant CAs at a dose of 2 mg As2O3 kg(-1) b.w. Similar induction was not evident at 4 mg As2O3 kg(-1) b.w. and exhibited antagonistic effect at 8 mg As2O3 kg(-1) b.w. To understand this differential effect, expression pattern of Nrf2 was observed. Nrf2 expression increased following As2O3 treatment in a dose-dependent manner up to 4 mg As2O3 kg(-1) b.w after which no further increase was noticed. NAC pre-treatment significantly reduced the extent of As2O3-induced CAs suggesting the protective role of...

Chemical communications (Cambridge, England), Jan 20, 2015

Several pyrene based fluorescent probes undergo lysine assisted monomer to excimer conversion in ... more Several pyrene based fluorescent probes undergo lysine assisted monomer to excimer conversion in a ratiometric manner. Intracellular lysine is detected using fluorescence microscopy.

Proceedings of the National Academy of Sciences of the United States of America, 1999

International journal of oncology, 2009

Mutation research, 1995

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences, 2013

Proceedings of the National Academy of Sciences, 1999

Molecular and Cellular Biology, 2009

Journal of Biological Chemistry, 1999

Developmental Biology, 2001

Acta Oceanologica Sinica, 2012

Http Dx Doi Org 10 1080 02772248 2013 862392, Dec 19, 2013

Journal of Fluorescence, 2015

Fluoride

Environmental Toxicology and Pharmacology, 2015

Inorganica Chimica Acta, 2015

Toxicology mechanisms and methods, Jan 23, 2015

Chemical communications (Cambridge, England), Jan 20, 2015