Mechanisms of cell death induction by L-amino acid oxidase, a major component of ophidian venom

Abstract

L-amino acid oxidase (LAAO) from the Malayan pit viper induces both necrosis and apoptosis in Jurkat cells. Cell death by necrosis is attributed to H 2 O 2 produced by oxidation of α-amino acids. In the presence of catalase that effectively scavenges H 2 O 2, a switch to apoptosis is observed. The major factors contributing to apoptosis are proposed to be: (i) generation of toxic intermediates from fetal calf serum (ii) binding and internalization of LAAO. The latter process appears to be mediated by the glycan moiety of the enzyme as desialylation reduces cytotoxicity. D-amino acid oxidase (DAAO), which catalyzes the same reaction as LAAO but lacks glycosylation, triggers necrosis as a consequence of H 2 O 2 production but not apoptosis in the presence of catalase. Thus induction of cell death by LAAO appears to involve both the generation of H 2 O 2 and the molecular interaction of the glycan moiety of the enzyme with structures at the cell surface.S. R. Ande, P. R. Kommoju contributed equally to this work.

Induction of apoptosis in yeast by L‐amino acid oxidase from the Malayan pit viper Calloselasma rhodostoma

“…In some venom this enzyme alone constitutes 30% of the total protein content (Zeller, 1977). Ophidian LAAOs catalyse the stereospecific oxidative deamination of L-amino acids to the corresponding α-keto acid, with a pronounced preference towards aromatic and hydrophobic amino acids, leucine and phenylalanine being among the best substrates 350 S. R. Ande et al (Ande et al, 2006). The reduced FAD co-factor is regenerated by reaction with dioxygen, leading to the formation of hydrogen peroxide, a known ROS with apoptotic potential, as mentioned previously.…”

“…Observations in cultured Jurkat cells indicated that hydrogen peroxide alone is not responsible for LAAO induced-apoptosis, as catalase can not fully rescue them (Ande et al, 2006). In order to further evaluate these possible contributions, we studied the interaction of LAAO with yeast cells.…”

“…In addition, LAAO exhibits antibacterial and antiviral properties, inhibiting the growth of both Gram-positive and -negative prokaryotes as well as HIV (Skarnes, 1970;Zhang et al, 2003Zhang et al, , 2004. Although the generation of hydrogen peroxide is necessary for the induction of apoptosis, it was suspected that glycosylation of LAAO contributes to this process by interaction of the bis-sialylated N -glycan moiety with structures on the cell surface (Ande et al, 2006;Suhr andKim, 1996, Du andClemetson, 2002).…”

Bothrops pirajai snake venom L-amino acid oxidase: in vitro effects on infection of Toxoplasma gondii in human foreskin fibroblasts

“…The probable mechanisms of cytotoxicity induced by LAAO involve necrosis, apoptosis, or depletion of essential amino acids in the culture medium by enzymatic oxidation (Butzke et al, 2005). The process of necrosis could be related to the direct action of hydrogen peroxide on the cell plasma membrane, since the mechanism of apoptosis in the development of morphological and biochemical changes leads to cell death (Ande et al, 2006). Therefore, most of the biological effects of LAAO may be due to the secondary effect of hydrogen peroxide generated during the specific catalytic activity (Ponnudurai et al, 1994).…”

Effect of L-lysine alpha-oxidase from Trichoderma cf. aureoviride Rifai BKMF-4268D on pheochromocytoma PC12 cell line

“…Suhr и Kim [15], которые исследовали оксидазу L-ААО из яда малайской гадюки, выдвинули предположение о том, что поскольку L-ААО является гликопротеином, важный вклад в индукцию клеточной смерти вносит взаимодействие её углеводного фрагмента с поверхностью клеток и создание высоких локальных концентраций H 2 O 2 , который тут же переносится в клетку, не подвергаясь действию внеклеточной каталазы; более того, авторы не исключают возможную интернализацию L-ААО клеткой. Ande с соавторами [16] [14].…”