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超氧化物歧化酶的过表达通过调节黑腹果蝇的细胞免疫系统来改善六价铬诱导的不良反应。

Over-expression of superoxide dismutase ameliorates Cr(VI) induced adverse effects via modulating cellular immune system of Drosophila melanogaster.

作者信息

Pragya Prakash, Shukla Arvind Kumar, Murthy Ramesh Chandra, Abdin Malik Zainul, Kar Chowdhuri Debapratim

机构信息

Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India ; Department of Biotechnology, Jamia Hamdard, New Delhi, India.

Analytical Section, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.

出版信息

PLoS One. 2014 Feb 4;9(2):e88181. doi: 10.1371/journal.pone.0088181. eCollection 2014.

Abstract

The evolutionarily conserved innate immune system plays critical role for maintaining the health of an organism. However, a number of environmental chemicals including metals are known to exert adverse effects on immune system. The present study assessed the in vivo effect of a major environmental chemical, Cr(VI), on cellular immune response using Drosophila melanogaster and subsequently the protective role of superoxide dismutase (SOD) based on the comparable performance of the tested anti-oxidant enzymes. The immuno-modulatory potential of Cr(VI) was demonstrated by observing a significant reduction in the total hemocyte count along with impaired phagocytic activity in exposed organism. Concurrently, a significant increase in the percentage of Annexin V-FITC positive cells, activation of DEVDase activity, generation of free radical species along with inhibition of anti-oxidant enzyme activities was observed in the hemocytes of exposed organism. In addition, we have shown that ONOO(-) is primarily responsible for Cr(VI) induced adverse effects on Drosophila hemocytes along with O2(-). While generation of O2(-)/ONOO(-) in Cr(VI) exposed Drosophila hemocytes was found to be responsible for the suppression of Drosophila cellular immune response, Cr(VI) induced alteration was significantly reduced by the over-expression of sod in Drosophila hemocytes. Overall, our results suggest that manipulation of one of the anti-oxidant genes, sod, benefits the organism from Cr(VI) induced alteration in cellular immunity. Further, this study demonstrates the applicability of D. melanogaster to examine the possible effects of environmental chemicals on innate immunity which can be extrapolated to higher organisms due to evolutionary conservation of innate immune system between Drosophila and mammals.

摘要

进化上保守的先天免疫系统对维持生物体的健康起着关键作用。然而,已知包括金属在内的多种环境化学物质会对免疫系统产生不利影响。本研究使用黑腹果蝇评估了一种主要环境化学物质六价铬(Cr(VI))对细胞免疫反应的体内影响,随后基于所测试的抗氧化酶的可比性能,研究了超氧化物歧化酶(SOD)的保护作用。通过观察暴露生物体中总血细胞计数的显著减少以及吞噬活性受损,证明了Cr(VI)的免疫调节潜力。同时,在暴露生物体的血细胞中观察到膜联蛋白V-FITC阳性细胞百分比显著增加、DEVDase活性激活、自由基产生以及抗氧化酶活性受到抑制。此外,我们已经表明,过氧亚硝酸盐(ONOO(-))与超氧阴离子(O2(-))一起主要负责Cr(VI)对果蝇血细胞的不利影响。虽然在暴露于Cr(VI)的果蝇血细胞中O2(-)/ONOO(-)的产生被发现是果蝇细胞免疫反应受到抑制的原因,但通过在果蝇血细胞中过表达sod,Cr(VI)诱导的改变显著减少。总体而言,我们的结果表明,操纵一种抗氧化基因sod可使生物体免受Cr(VI)诱导的细胞免疫改变的影响。此外,本研究证明了黑腹果蝇在检测环境化学物质对先天免疫可能影响方面的适用性,由于果蝇和哺乳动物之间先天免疫系统的进化保守性,这些影响可以外推到高等生物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/3913750/48f6c29303a1/pone.0088181.g001.jpg

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