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. (11th May 2014)

• Record Type: Journal Article
• Authors: Mendivil-Perez, Miguel; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos
• Other Names: Calabrese Vittorio Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2014(2014)
• Publication Date: 2014-05-11
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2014/457154
• Languages: English
• ISSNs: 1942-0900

Abstract

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 (O 2 ∙ -, 68%)/hydrogen peroxide (H2 O2, 54%), activation of NF-κ 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 (Δ Ψ m, 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/H2 O2 -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.