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Characterisation of Anopheles gambiae heme oxygenase and metalloporphyrin feeding suggests a potential role in reproduction.

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Spencer, Christopher, YuntaYanes, Cristina, Gomes de Lima, Glauber Pacelli, Hemmings, Kay, Lian, Lu-Yun, Lycett, Gareth ORCID: https://orcid.org/0000-0002-2422-053X and Paine, Mark ORCID: https://orcid.org/0000-0003-2061-7713 (2018) 'Characterisation of Anopheles gambiae heme oxygenase and metalloporphyrin feeding suggests a potential role in reproduction.'. Insect Biochemistry and Molecular Biology, Vol 98, pp. 25-33.

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Abstract

The mosquito Anopheles gambiae is the principal vector for malaria in sub-Saharan Africa. The ability of A. gambiae to transmit malaria is strictly related to blood feeding and digestion, which releases nutrients for oogenesis, as well as substantial amounts of highly toxic free heme. Heme degradation by heme oxygenase (HO) is a common protective mechanism, and a gene for HO exists in the An. gambiae genome HO (AgHO), although it has yet to be functionally examined. Here, we have cloned and expressed An. gambiae HO (AgHO) in E. coli. Purified recombinant AgHO bound hemin stoichiometrically to form a hemin-enzyme complex similar to other HOs, with a K of 3.9 ± 0.6 μM; comparable to mammalian and bacterial HOs, but 7-fold lower than that of Drosophila melanogaster HO. AgHO also degraded hemin to biliverdin and released CO and iron in the presence of NADPH cytochrome P450 oxidoreductase (CPR). Optimal AgHO activity was observed at 27.5 °C and pH 7.5. To investigate effects of AgHO inhibition, adult female A. gambiae were fed heme analogues Sn- and Zn-protoporphyrins (SnPP and ZnPP), known to inhibit HO. These led to a dose dependent decrease in oviposition. Cu-protoporphyrin (CuPP), which does not inhibit HO had no effect. These results demonstrate that AgHO is a catalytically active HO and that it may play a key role in egg production in mosquitoes. It also presents a potential target for the development of compounds aimed at sterilising mosquitoes for vector control.

Item Type: Article
Subjects: QX Parasitology > QX 20 Research (General)
QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1016/j.ibmb.2018.04.010
Depositing User: Stacy Murtagh
Date Deposited: 17 May 2018 09:39
Last Modified: 03 May 2019 01:02
URI: http://archive.lstmed.ac.uk/id/eprint/8628

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