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Extracellular and cytoplasmic CuZn superoxide dismutases from Brugia lymphatic filarial nematode parasites.

Abstract：

:We have isolated full-length cDNAs encoding two distinct types of CuZn superoxide dismutases (SODs) from the filarial nematode parasite Brugia pahangi. The derived amino acid sequences suggested that one class of cDNAs represented a cytoplasmic form of SOD and the second class represented an extracellular (EC) variant. The predicted proteins were highly homologous to each other, but the sequence of the latter contained an additional 43 residues at the N terminus, the first 16 of which were markedly hydrophobic, and four potential sites for N-linked glycosylation. Western blotting (immunoblotting) with an antiserum to a partial SOD expressed in Escherichia coli revealed two proteins with estimated molecular masses of 19 and 29 kDa. Digestion with N-glycanase indicated that the latter protein corresponded to the EC form, as it possessed N-linked oligosaccharide chains at three sites, leaving a peptide backbone with an estimated molecular mass of 22 kDa, which was consistent with the additional 27 amino acids predicted from the cDNA sequence. Gel filtration indicated that both enzymes were dimeric in their native forms, in contrast to the human EC-SOD, which is tetrameric. Comparison of the primary structure of the parasite EC-SOD with that of the human EC enzyme revealed two major differences: the N-terminal extension of the parasite enzyme was shorter by 25 residues, and it also lacked the C-terminal charged extension which mediates binding to cell surface sulfated proteoglycans. Lavage of Mongolian jirds infected intraperitoneally with Brugia malayi resulted in the recovery of filarial CuZn SODs, principally the EC form, indicating that this form of SOD is secreted in vivo. This EC enzyme may contribute to parasite persistence by neutralizing superoxide generated by activated leukocytes, thus acting as both an antioxidant and an anti-inflammatory factor.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Tang L,Ou X,Henkle-Dührsen K,Selkirk ME

doi

10.1128/IAI.62.3.961-967.1994

subject

Has Abstract

pub_date

1994-03-01 00:00:00

pages

961-7

issue

eissn

0019-9567

issn

1098-5522

journal_volume

pub_type

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Extracellular and cytoplasmic CuZn superoxide dismutases from Brugia lymphatic filarial nematode parasites.