Biomedical subjects

Anupam Pradhan

Publications and source records attributed to Anupam Pradhan.

2 recordsLinked to original sources

PubMed2005

Alterations in bronchoalveolar lavage constituents, oxidant/antioxidant status, and lung histology following intratracheal instillation of respirable suspended particulate matter.

Urban suspended particulate pollutants differ with place of occurrence, meteorological conditions, physicochemical compositions, and the response of the bronchopulmonary apparatus. Lung injury following intratracheal instillation of respirable suspended particulate matter (RSPM) collected in an urban setting in India was investigated in rats. The animals were killed 15 days after exposure to 2.5, 5.0, and 10.0 mg of RSPM. We examined the changes in lung histology, enzymatic activity in the bronchoalveolar lavage (BAL), and the oxidant/ antioxidant status in lung homogenates. The alterations in these parameters were compared with those in rats instilled with quartz particulates, which were used as positive controls. Exposure to RSPM resulted in an increase in the relative weight of lungs and inflammatory changes evidenced by an increase in the total cellularity of the lungs, predominantly polymorphonuclear cells, demonstrable both in the lungs sections and in the bronchoalveolar lavage of the exposed animals. An increase in the protein content and in the lactate dehydrogenase activity in the BAL was found in the RSPM-exposed rats. A marked increase in the output of lipid peroxides and a dose-dependent increase in the formation of reactive nitrogen species (NO) in lung homogenates and BAL, respectively, was found in the RSPM-exposed rats. A significant decrease in the enzymatic lung antioxidants, superoxide dismutase, and catalase was observed. However, the alterations in the levels of glutathione in the lungs of the RSPM-exposed animals were not significant. The inflammatory reaction, oxidative changes, and enzyme release, were more marked in quartz-exposed animals in comparison to the RSPM-exposed rats.

Air Pollutants↗

PubMed2004

An alpha-proteobacterial type malate dehydrogenase may complement LDH function in Plasmodium falciparum. Cloning and biochemical characterization of the enzyme.

Malate dehydrogenase (MDH) may be important in carbohydrate and energy metabolism in malarial parasites. The cDNA corresponding to the MDH gene, identified on chromosome 6 of the Plasmodium falciparum genome, was amplified by RT-PCR, cloned and overexpressed in Escherichia coli. The recombinant Pf MDH was purified to homogeneity and biochemically characterized as an NAD(+)(H)-specific MDH, which catalysed reversible interconversion of malate to oxaloacetate. Pf MDH could not use NADP/NADPH as a cofactor, but used acetylpyridine adenine dinucleoide, an analogue of NAD. The enzyme exhibited strict substrate and cofactor specificity. The highest levels of Pf MDH transcripts were detected in trophozoites while the Pf MDH protein level remained high in trophozoites as well as schizonts. A highly refined model of Pf MDH revealed distinct structural characteristics of substrate and cofactor binding sites and important amino acid residues lining these pockets. The active site amino acid residues involved in substrate binding were conserved in Pf MDH but the N-terminal glycine motif, which is involved in nucleotide binding, was similar to the GXGXXG signature sequence found in Pf LDH and also in alpha-proteobacterial MDHs. Oxamic acid did not inhibit Pf MDH, while gossypol, which interacts at the nucleotide binding site of oxidoreductases and shows antimalarial activity, inhibited Pf MDH also. Treatment of a synchronized culture of P. falciparum trophozoites with gossypol caused induction in expression of Pf MDH, while expression of Pf LDH was reduced and expression of malate:quinone oxidoreductase remained unchanged. Pf MDH may complement Pf LDH function of NAD/NADH coupling in malaria parasites. Thus, dual inhibitors of Pf MDH and Pf LDH may be required to target this pathway and to develop potential new antimalarial drugs.

Amino Acid Sequence↗