Purification and Cloning of an Apoptosis-Inducing Protein Derived from Fish Infected with <i>Anisakis simplex</i>, a Causative Nematode of Human Anisakiasis

Jung, Sang-Kee; Mai, Angela; Iwamoto, Mitsunori; Arizono, Naoki; Fujimoto, Daisaburo; Sakamaki, Kazuhiro; Yonehara, Shin

doi:10.4049/jimmunol.165.3.1491

Cited by 57 publications

(52 citation statements)

References 27 publications

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“…Fish react to Anisakis by producing apoptosis-inducing proteins in infected tissues ( Jung et al 2000), suggesting that Anisakis can seriously hamper fish health. Salmonids do not show parental care, and since males provide only genes for the offspring, indirect genetic benefits may be particularly important in this family.…”

Section: Discussionmentioning

confidence: 99%

MHC-mediated mate choice increases parasite resistance in salmon

2008

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Natural (parasite-driven) and sexual selection are thought to maintain high polymorphism in the genes of the major histocompatibility complex (MHC), but support for a link between mate choice, MHC variation and increased parasite resistance is circumstantial. We compared MHC diversity and Anisakis loads among anadromous Atlantic salmon (Salmo salar L.) returning to four rivers to spawn, which had originated from natural spawning (parents allowed to mate freely) or artificial crosses (parents deprived from the potential benefits of mate choice). We found that the offspring of artificially bred salmon had higher parasite loads and were almost four times more likely to be infected than free-mating salmon, despite having similar levels of MHC diversity. Moreover, the offspring of wild salmon were more MHC dissimilar than the offspring of artificially crossed salmon, and uninfected fish were more dissimilar for MHC than infected fish. Thus, our results suggest a link between disassortative mating and offspring benefits and indicate that MHC-mediated mate choice and natural (parasite-driven) selection act in combination to maintain MHC diversity, and hence fitness. Therefore, artificial breeding programmes that negate the potential genetic benefits of mate choice may result in inherently inferior offspring, regardless of population size, rearing conditions or genetic diversity.

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Section: Discussionmentioning

confidence: 99%

MHC-mediated mate choice increases parasite resistance in salmon

2008

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“…The apoptosisinducing activity of the purified recombinant AIP was compared with that of native AIP purified from mackerels infected with Anisakis. 12 Figure 1C clearly shows the recombinant AIP to possess the same specific activity as that of native AIP.…”

Section: Expression and Puri®cation Of Recombinant Aip Proteinmentioning

confidence: 93%

“…Since AIP produces H 2 O 2 by disrupting L-lysine as a main substrate, 12 which is an essential amino acid, we postulated that the delayed apoptosis induced by AIP is caused by rapid depletion of L-lysine from the medium. Then, we analyzed the effect of an excess of L-lysine on AIP-induced delayed apoptosis.…”

Section: Aip-induced Delayed Apoptosis Is Mediated By Depletion Of L-mentioning

confidence: 99%

“…In fact, AIP showed LAO activity, producing H 2 O 2 by oxidizing several L-amino acids including L-lysine. 12 To elucidate whether the apoptosis-inducing activity of AIP is associated with LAO activity, we quantified AIP-induced H 2 O 2 in RPMI 1640 medium. When the medium was incubated with AIP at 100 ng/ml, more than 80 mM H 2 O 2 was produced within 2 h (Figure 2A), which is enough to induce apoptosis in HL-60 cells (data not shown).…”

Section: Aip-induced Fast Apoptosis Is Mediated By H 2 Omentioning

confidence: 99%

“…We recently cloned a novel apoptosisinducing protein (AIP) from Anisakis-infected mackerels which is homologous in structure to LAO, 12 and this protein is also capable of generating H 2 O 2 in vitro by catalyzing the oxidation of some L-amino acids, especially L-lysine, indicating that AIP belongs to LAO family. Because AIP was specifically purified from fluid in capsules where parasites were confined in vermiculose mackerels, AIP was speculated to be involved in defense against parasites, but its actual role is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Apoptosis-inducing protein, AIP, from parasite-infected fish induces apoptosis in mammalian cells by two different molecular mechanisms

et al. 2001

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AIP (apoptosis-inducing protein) is a protein purified and cloned from Chub mackerel infected with the larval nematode, Anisakis simplex, which induces apoptosis in various mammalian cells including human tumor cell lines. AIP has shown structural and functional homology to Lamino acid oxidase (LAO) which oxidizes several L-amino acids including L-lysine and AIP-induced apoptosis has been suggested to be mediated by H 2 O 2 generated by LAO activity of AIP. In this study, we confirmed that recombinant AIP generated enough H 2 O 2 in culture medium to induce rapid apoptosis in cells and this apoptosis was clearly inhibited by co-cultivation with antioxidants such as catalase and Nacetyl-cysteine. Surprisingly, however, we found that AIP still could induce H 2 O 2 -independent apoptosis more slowly than H 2 O 2 -dependent one in HL-60 cells even in the presence of antioxidants. In addition, the HL-60-derived cell line HP100-1, which is a H 2 O 2 -resistant variant, underwent apoptosis on treatment with AIP with a similar delayed time course. The latter apoptosis was completely blocked by addition of L-lysine to the culture medium, which is the best substrate of AIP as LAO, indicating that decreased concentration of L-lysine in the culture medium by AIPtreatment induced apoptosis. We also showed that the both apoptosis by AIP were associated with the release of cytochrome c from mitochondria and activation of caspase-9, and overexpressed Bcl-2 could inhibit both of the AIPinduced apoptosis. These results indicate that AIP induces apoptosis in cells by two distinct mechanisms; one rapid and mediated by H 2 O 2 , the other delayed and mediated by deprivation of L-lysine, both of which utilize caspase-9/ cytochrome c system. Cell Death and Differentiation (2001) 8, 298 ± 307.

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The Chemistry of Escapin: Identification and Quantification of the Components in the Complex Mixture Generated by an L‐Amino Acid Oxidase in the Defensive Secretion of the Sea Snail Aplysia californica

Kamio

Zheng

et al. 2009

Chemistry A European J

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Escapin is an L-amino acid oxidase in the ink of a marine snail, the sea hare Aplysia californica, which oxidizes L-lysine (1) to produce a mixture of chemicals which is antipredatory and antimicrobial. The goal of our study was to determine the identity and relative abundance of the constituents of this mixture, using molecules generated enzymatically with escapin and also using products of organic syntheses. We examined this mixture under the natural range of pH values for ink-from approximately 5 at full strength to approximately 8 when fully diluted in sea water. The enzymatic reaction likely forms an equilibrium mixture containing the linear form alpha-keto-epsilon-aminocaproic acid (2), the cyclic imine Delta(1)-piperidine-2-carboxylic acid (3), the cyclic enamine Delta(2)-piperidine-2-carboxylic acid (4), possibly the linear enol 6-amino-2-hydroxy-hex-2-enoic acid (7), the alpha-dihydroxy acid 6-amino-2,2-dihydroxy-hexanoic acid (8), and the cyclic aminol 2-hydroxy-piperidine-2-carboxylic acid (9). Using NMR and mass spectroscopy, we show that 3 is the major component of this enzymatic product at any pH, but at more basic conditions, the equilibrium shifts to produce relatively more 4, and at acidic conditions, the equilibrium shifts to produce relatively more 2, 7, and/or 9. Studies of escapin's enzyme kinetics demonstrate that because of the high concentrations of escapin and L-lysine in the ink secretion, millimolar concentrations of 3, H(2)O(2), and ammonia are produced, and also lower concentrations of 2, 4, 7, and 9 as a result. We also show that reactions of this mixture with H(2)O(2) produce delta-aminovaleric acid (5) and delta-valerolactam (6), with 6 being the dominant component under the naturally acidic conditions of ink. Thus, the product of escapin's action on L-lysine contains an equilibrium mixture that is more complex than previously known for any L-amino acid oxidase.

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Purification and Cloning of an Apoptosis-Inducing Protein Derived from Fish Infected with Anisakis simplex, a Causative Nematode of Human Anisakiasis

Cited by 57 publications

References 27 publications

MHC-mediated mate choice increases parasite resistance in salmon

MHC-mediated mate choice increases parasite resistance in salmon

Apoptosis-inducing protein, AIP, from parasite-infected fish induces apoptosis in mammalian cells by two different molecular mechanisms

The Chemistry of Escapin: Identification and Quantification of the Components in the Complex Mixture Generated by an L‐Amino Acid Oxidase in the Defensive Secretion of the Sea Snail Aplysia californica

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