L-amino acid oxidase isolated from Micrurus mipartitus snake venom (MipLAAO) specifically induces apoptosis in acute lymphoblastic leukemia cells mostly via oxidative stress-dependent signaling mechanism.

Abstract

The effect of Micrurus mipartitus snake venom as a therapeutic alternative for T-acute lymphoblastic leukemia (ALL) is still unknown. This study was aimed to evaluate the cytotoxic effect of M. mipartitus snake venom and a new L-amino acid oxidase (LAAO), named MipLAAO, on human peripheral blood lymphocytes (PBL) and on T-ALL cells (Jurkat), and its mechanism of action. PBL and Jurkat cells were treated with venom and MipLAAO, and morphological changes in the cell nucleus/DNA, mitochondrial membrane potential, levels of intracellular reactive oxygen species and cellular apoptosis markers were determined by fluorescence microscopy, flow cytometry and pharmacological inhibition. Venom and MipLAAO induced apoptotic cell death in Jurkat cells, but not in PBL, in a dose-response manner. Additionally, venom and MipLAAO increased dichlorofluorescein fluorescence intensity, indicative of H2O2 production, increased DJ-1 Cys106-sulfonate, as a marker of intracellular stress and induced the up-regulation of PUMA, p53 and phosphorylation of c-JUN. Additionally, it increased the expression of apoptotic CASPASE-3. In conclusion, M. mipartitus venom and MipLAAO selectively induces apoptosis in Jurkat cells through a H2O2-mediated signaling pathway dependent mostly on CASPASE-3 pathway. Our findings support the potential use of M. mipartitus snake venom compounds as a potential treatment for T-ALL.

• Authors: Jesus Bedoya-Medina, Miguel Mendivil-Perez, Paola Rey-Suarez, Marlene Jimenez-Del-Rio, Vitelbina Núñez, Carlos Velez-Pardo
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 134 Pg. 1052-1062 (Aug 01 2019) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 31129208 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Reactive Oxygen Species
• Snake Venoms
• Hydrogen Peroxide
• L-Amino Acid Oxidase

Topics

• Animals
• Apoptosis (drug effects)
• Biomarkers, Tumor
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chromatography, High Pressure Liquid
• Coral Snakes
• Humans
• Hydrogen Peroxide (metabolism)
• Jurkat Cells
• L-Amino Acid Oxidase (chemistry, isolation & purification, pharmacology)
• Membrane Potential, Mitochondrial (drug effects)
• Oxidative Stress (drug effects)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Reactive Oxygen Species
• Signal Transduction (drug effects)
• Snake Venoms (enzymology)