Recent evidence established a crucial role for mammalian oxygen sensing transcription factor hypoxia inducible factor-1 (HIF-1) in innate immunity against intracellular pathogens. In response to most of these pathogens host phagocytes increase transcription of HIF-1α, the regulatory component of HIF-1 to express various effector molecules against invaders. Leishmania donovani (LD), a protozoan parasite and the causative agent of fatal visceral leishmaniasis resides in macrophages within mammalian host. The mechanism of HIF-1 activation or its role in determining the fate of LD in infected macrophages is still not known. To determine that J774 macrophages were infected with LD and about four-fold increase in HIF-1 activity and HIF-1α expression were detected. A strong increase in HIF-1α expression and nuclear localization was also detected in LD-infected J774 cells, peritoneal macrophages and spleen derived macrophages of LD-infected BALB/c mice. A two-fold increase in HIF-1α mRNA was detected in LD-infected macrophages suggesting involvement of a transcriptional mechanism that was confirmed by promoter activity. We further revealed that LD also induced HIF-1α expression by depleting host cellular iron pool to affect prolyl hydroxylase activity resulting in to stabilization of HIF-1α. To determine the role of HIF-1 on intracellular LD, cells were transfected with HIF-1α siRNA to attenuate its expression and then infected with LD. Although, initial infection rate of LD in HIF-1α attenuated cells was not affected but intracellular growth of LD was significantly inhibited; while, over-expression of stabilized form of HIF-1α promoted intracellular growth of LD in host macrophage. Our results strongly suggest that LD activates HIF-1 by dual mechanism for its survival advantage within macrophage.
Abstract.A mucopolysaccharide, chitosan was grafted with polyaniline through oxidative-radical copolymerization using ammonium persulfate in acidic medium. The grafting conditions were extensively studied by varying grafting parameters. All the findings have been discussed and proposed a plausible mechanism for the graft copolymerization. The representative chitosan-graft-polyaniline (Ch-g-PANI) was characterized using UV-vis, FTIR, TGA, X-ray diffraction and Scanning electron microscopy taking chitosan as reference. Ch-g-PANI exhibited electrical conductivity, which increases with the extent of grafting onto chitosan backbone. Its electrical conductivity is further influenced by pH and showed pH switching electrical conduction behavior when exposed to NN3/HCl vapors. The application of conducting biomaterial such as Ch-g-PANI in the electronic devices especially for the fabrication of sensor devices would be attractive not only in terms of product cost and environmental safety but also from a materials science point of view.
Using microwave (MW) irradiation, polyacrylonitrile was grafted onto chitosan with 170% grafting yield under homogeneous conditions in 1.5 min in the bsence of any radical initiator or catalyst. Under similar conditions a maximum grafting of 105% could be achieved when the K 2 S 2 O 8 /ascorbic acid redox system was used as radical initiator in a thermostatic water bath at 35 Ϯ 2°C. The representative graft copolymer was characterized by Fourier transform infrared spectra, thermogravimetric analysis, and X-ray diffraction measurement, taking chitosan as a reference. The effects of such reaction variables as monomer/ chitosan concentration, MW power, and exposure time on the graft co polymerization were studied. A probable mechanism for grafting without the redox system under microwaves was proposed.
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