Cover Picture: 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 SnailAplysia californica(Chem. Eur. J. 7/2009)

Abstract The anti-tumor potential of animal toxins has fully attracted the attention of researchers. Snake venoms is a complex mixture of different components and has revealed high toxicity on normal and tumoral tissues or cells. The snake venom L-Amino-acid oxidase (svLAAO) has grown up to be a critical research target in molecular biology sciences and medicine sciences since widespread presence and various biological roles, including antitumor application. We found that Crotalus adamanteus (C. adamanteus) venom LAAO significantly decreased the viability of ovarian cancer cells and caused morphological changes preceded cell death. Cell experiments confirmed that C. adamanteus venom LAAO caused alterations of intrinsic or extrinsic apoptosis pathway-related genes in ovarian cancer cells. Animal experiments and histological analysis also proved that C. adamanteus venom LAAO could effectively inhibit the damage of ovarian cancer to tissues. The major apoptosis induction of C. adamanteus venom LAAO on ovarian cancer cells can be blocked by catalase, suggesting that the cytotoxicity of C. adamanteus venom LAAO on ovarian cancer cells was mainly mediated by H2O2. Our preliminary results revealed that C. adamanteus venom LAAO may induce apoptosis of ovarian cancer cells through the death receptor pathway and mitochondrial pathway. It is inferred that C. adamanteus venom LAAO will be some advantages in New Drug Research and Development of antitumor drugs in the future. Nevertheless, extra studies on the pharmacological actions and molecular mechanism of svLAAO in anti-cancer are necessary in order to better promote its application.

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Purification and Characterization of Lupus Anticoagulant Like Protein from Agkistrodon Halys Brevicaudus Venom

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650698 ◽

1996 ◽

Vol 76 (06) ◽

pp. 0993-0997

Author(s):

Zhao-Yan Li ◽

Xiao-Wei Wu ◽

Tie-Fu Yu ◽

Eric C-Y Lian

Keyword(s):

Amino Acid ◽

Lupus Anticoagulant ◽

Inhibitory Effect ◽

Clotting Factor ◽

Acid Oxidase ◽

Crude Venom ◽

Amino Acid Oxidase ◽

Sds Page ◽

The Individual ◽

Reducing Condition

SummaryBy means of CM-Sephadex C-25, DEAE-Sephadex A-50, Sephadex G-200, and Sephadex G-75 chromatographies, a lupus anticoagulant like protein (LALP) from Agkistrodon halys brevicaudus was purified. On SDS-PAGE, the purified LALP had a molecular weight of 25,500 daltons under non-reducing condition and 15,000 daltons under reducing condition. The isoelectric point was pH 5.6. Its N terminal amino acid sequencing revealed a mixture of 2 sequences: DCP(P/S)(D/G)WSSYEGH(C/R)Q(Q/K). It was devoid of phospho-lipaseA, fibrino(geno)lytic, 5′-nucleotidase, L-amino acid oxidase, phosphomonoesterase, phosphodiesterase and thrombin-like activities, which were found in crude venom. In the presence of LALP, PT, aPTT, and dRVVT of human plasma were markedly prolonged and its effects were concentration-dependent but time-independent. The inhibitory effect of LALP on the plasma clotting time was enhanced by decreasing phospholipid concentration in TTI test. The individual clotting factor activity was not affected by LALP when higher dilutions of LALP-plasma mixture were used for assay. Russell’s viper venom time was shortened when high phospholipid confirmatory reagent was used. Therefore, the protein has lupus anticoagulant property.

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Impairment of Platelet Aggregation by Echis colorata Venom Mediated by L-Amino Acid Oxidase or H2O2

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657280 ◽

1982 ◽

Vol 48 (03) ◽

pp. 277-282 ◽

Cited By ~ 22

Author(s):

I Nathan ◽

A Dvilansky ◽

T Yirmiyahu ◽

M Aharon ◽

A Livne

Keyword(s):

Hydrogen Peroxide ◽

Amino Acid ◽

Platelet Aggregation ◽

Snake Venom ◽

Oxidase Activity ◽

Enzyme Preparation ◽

Acid Oxidase ◽

Crude Venom ◽

Amino Acid Oxidase ◽

Hemostatic Disorders

SummaryEchis colorata bites cause impairment of platelet aggregation and hemostatic disorders. The mechanism by which the snake venom inhibits platelet aggregation was studied. Upon fractionation, aggregation impairment activity and L-amino acid oxidase activity were similarly separated from the crude venom, unlike other venom enzymes. Preparations of L-amino acid oxidase from E.colorata and from Crotalus adamanteus replaced effectively the crude E.colorata venom in impairment of platelet aggregation. Furthermore, different treatments known to inhibit L-amino acid oxidase reduced in parallel the oxidase activity and the impairment potency of both the venom and the enzyme preparation. H2O2 mimicked characteristically the impairment effects of L-amino acid oxidase and the venom. Catalase completely abolished the impairment effects of the enzyme and the venom. It is concluded that hydrogen peroxide formed by the venom L-amino acid oxidase plays a role in affecting platelet aggregation and thus could contribute to the extended bleeding typical to persons bitten by E.colorata.

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Faculty Opinions recommendation of Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1010617.193306 ◽

2003 ◽

Author(s):

Michael O'Donovan

Keyword(s):

Amino Acid ◽

Human Gene ◽

Physiological Data ◽

Acid Oxidase ◽

Amino Acid Oxidase

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Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat

Pharmacological Reports ◽

10.1007/s43440-020-00207-x ◽

2021 ◽

Author(s):

Hong Wei ◽

Zuyue Chen ◽

Ari Koivisto ◽

Antti Pertovaara

Keyword(s):

Amino Acid ◽

Nmda Receptors ◽

Receptor Antagonist ◽

Gap Junction ◽

Male Rats ◽

Acid Oxidase ◽

Amino Acid Oxidase ◽

Mk 801 ◽

Mechanical Hypersensitivity ◽

Pain Hypersensitivity

Abstract Background Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, σ1 and NMDA receptors, gap junctions and D-amino acid oxidase. Methods Experiments were performed in adult male rats with a chronic intrathecal catheter for spinal drug administrations. Mechanical nociception was assessed with monofilaments and heat nociception with radiant heat. N,N-dimethylsphingosine (DMS) was administered to induce pain hypersensitivity. Ononetin, isosakuranetin, naringenin (TRPM3 antagonists), BD-1047 (σ1 receptor antagonist), carbenoxolone (a gap junction decoupler), MK-801 (NMDA receptor antagonist) and AS-057278 (inhibitor of D-amino acid oxidase, DAAO) were used to prevent the DMS-induced hypersensitivity, and pregnenolone sulphate (TRPM3 agonist) to recapitulate hypersensitivity. Results DMS alone produced within 15 min a dose-related mechanical hypersensitivity that lasted at least 24 h, without effect on heat nociception. Preemptive treatments with ononetin, isosakuranetin, naringenin, BD-1047, carbenoxolone, MK-801 or AS-057278 attenuated the development of the DMS-induced hypersensitivity, but had no effects when administered alone. Pregnenolone sulphate (TRPM3 agonist) alone induced a dose-related mechanical hypersensitivity that was prevented by ononetin, isosakuranetin and naringenin. Conclusions Among spinal pronociceptive mechanisms activated by DMS are TRPM3, gap junction coupling, the σ1 and NMDA receptors, and DAAO.

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