Study on the Effects of Copper and its Regulatory Genes on Leishmania Major Infections

Zahrana, Fathima (2019) Study on the Effects of Copper and its Regulatory Genes on Leishmania Major Infections. Masters thesis, Indian Institute of Science Education and Research Kolkata.

PDF (MS dissertation of Fathima Zahrana (14MS013)) 14MS013.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

Copper is an essential micronutrient for cells. It is extremely essential as a key cofactor for several enzymes because of its redox ability to switch between it Cu⁺ and Cu²⁺ states. Copper is required for cytochrome c oxidase, ceruloplasmin, and others which are essential for the normal functioning of the cell. However the amount of copper in the cell needs to be tightly regulated as it can through Fenton-like chemistry produce toxic ROS species which can damage the cells. Copper transporters in addition to secretory and export functions are also involved in host defense against bacterial and fungal pathogens. Previous literature studies have shown upregulation of copper transporters, ATP7A, a 165 kDa P-type ATPase is involved in host defense against pathogens. Another copper regulatory protein CTR1 was also shown to be upregulated as a response against infection implying copper transporters are involved in host defense against bacteria and fungi. My study is focused on how copper regulators are modulated with respect to infection of higher eukaryotic intracellular obligate parasite such as Leishmania major infections in macrophages. For this I had performed RT PCR to see upregulation of copper transporters and chaperones and have successfully showed upregulation of ATP7A, CTR1 and CTR2 thereby showing copper transporters may play roles in macrophage defense against the parasite. Also, I have through immunofluorescence studies tried to identify a possible pathway that ATP7A follows as a consequence of L. major infections in J774A.1 murine macrophages.

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