Response to Rotenone Is Glucose-Sensitive in a Model of Human Acute Lymphoblastic Leukemia: Involvement of Oxidative Stress Mechanism, DJ-1, Parkin, and PINK-1 Proteins

ABSTRACT: To establish the effect of low (11 mM) and high (55 mM) glucose concentrations (G11, G55) on Jurkat cells exposed to rotenone (ROT, a class 5 mitocan). We demonstrated that ROT induces apoptosis in Jurkat cells cultured in G11 by oxidative stress (OS) mechanism involving the generation of anion superoxide radical (, 68%)/hydrogen peroxide (H2O2, 54%), activation of NF-B (32%), p53 (25%), c-Jun (17%) transcription factors, and caspase-3 (28%), apoptosis-inducing factor (AIF, 36%) nuclei translocation, c-Jun N-terminal kinase (JNK) activation, and loss of mitochondria transmembrane potential (, 62%) leading to nuclei fragmentation (~10% and ~40% stage I-II fragmented nuclei, resp.). ROT induces massive cytoplasmic aggregates of DJ-1 (93%), and upregulation of Parkin compared to untreated cells, but no effect on PINK-1 protein was observed. Cell death marker detection and DJ-1 and Parkin expression were significantly reduced when cells were cultured in G55 plus ROT. Remarkably, metformin sensitized Jurkat cells against ROT in G55. Our results indicate that a high-glucose milieu promotes resistance against ROT/H2O2-induced apoptosis in Jurkat cells. Our data suggest that combined therapy by using mitochondria-targeted damaging compounds and regulation of glucose (e.g., metformin) can efficiently terminate leukemia cells via apoptosis in hyperglycemic conditions.

• Autores: Mendivil Pérez, Miguel Ángel; Jiménez del Río, Marlene; Vélez Pardo, Carlos Alberto
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2014
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/38549
• Acceso en línea: https://hdl.handle.net/10495/38549
• Palabra clave: Apoptosis; Caspase 3; Peróxido de Hidrógeno; Hydrogen Peroxide; Forma del Núcleo Celular - efectos de los fármacos; Cell Nucleus Shape - drug effects; Activación Enzimática - efectos de los fármacos; Enzyme Activation - drug effects; Péptidos y Proteínas de Señalización Intracelular; Intracellular Signaling Peptides and Proteins; Membrane Potential, Mitochondrial - drug effects; Membrane Potential, Mitochondrial - drug effects; Leucemia-Linfoma Linfoblástico de Células Precursoras; Precursor Cell Lymphoblastic Leukemia-Lymphoma; https://id.nlm.nih.gov/mesh/D017209; https://id.nlm.nih.gov/mesh/D053148; https://id.nlm.nih.gov/mesh/D006861; https://id.nlm.nih.gov/mesh/D053144; https://id.nlm.nih.gov/mesh/D004789; https://id.nlm.nih.gov/mesh/D047908; https://id.nlm.nih.gov/mesh/D053078; https://id.nlm.nih.gov/mesh/D054198
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/