Depletion of Glutathione by Buthionine Sulfoximine Is Cytotoxic for Human Neuroblastoma Cell Lines via Apoptosis

Anderson, Clarke P.; Tsai, J; Meek, William E.; Liu, R.-M.; Tang, Yongmin; Forman, Henry Jay; Reynolds, C. Patrick

doi:10.1006/excr.1998.4303

Cited by 100 publications

(80 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…BSO is a specific ␥-glutamylcysteine synthetase inhibitor that blocks the rate-limiting step of GSH biosynthesis and depletes the intracellular GSH pool in both cultured cells and whole animals (18,36,37). We consistently observed that 6 mM BSO significantly reduced the GSH level and the GSH:GSSG ratio by 90 and 60%, respectively, compared with the control level (p Ͻ 0.001) (Fig.…”

Section: Role Of Redox Homeostasis In Hyperoxia Tolerance-tomentioning

confidence: 60%

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

Zhao¹,

Zhou²,

Haddad

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

It is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMPs) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e.g. Diptericin) allows wild-type flies to survive much better in hyperoxia. In this study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with AMP overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS levels after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that 1) AMPs play an important role in tolerance to oxidant stress, 2) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and 3) this change in redox balance plays an important role in survival in hyperoxia.Oxygen is essential for aerobic life. However, except for the beneficial role in wound healing, too little or too much oxygen can induce morbidity and mortality (1, 2). Mammalian aging and numerous diseases such as neurodegenerative diseases and chronic inflammatory diseases, as well as injury to the heart, lungs, retina, brain, and other organs due to ischemia and reperfusion states, result, by and large, from oxidant injury (3-6). High O 2 -induced oxidant injury could occur in cells in every organ, especially in the lungs, retina, heart, and brain (7,8). Prolonged exposure to high O 2 generates excessive reactive oxygen species (ROS), 2 induces cell death and oxidative stress responses, affects the immune response and DNA integrity, and modulates cell growth (5, 9 -11).Drosophila melanogaster has similar O 2 response pathways as mammals, and research on flies has enhanced our understanding of oxidant stress (12)(13)(14). In the past, through an experimental selection design over many generations, we have successfully generated D. melanogaster flies that tolerate tremendously high O 2 -induced oxidative stress. Microarray analysis has revealed that the family of antimicrobial peptides (AMPs) is over-represented among the up-regulated genes in these tolerant flies. We have further demonstrated that overexpression of even one AMP gene at a time (e.g. Diptericin (Dpt)) allows wild-type flies to survive much better in hyperoxia (15). To our knowledge, this is t...

show abstract

Section: Role Of Redox Homeostasis In Hyperoxia Tolerance-tomentioning

confidence: 60%

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

Zhao¹,

Zhou²,

Haddad

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…On the contrary, depletion of GSH by BSO sensitizes SH-SY5Y cells to diamide and activates apoptosis via the p38 MAPK /p53-mediated signaling pathway. It has been exhaustively reported that BSO enhances apoptotic response of neuroblastoma to different stimuli by increasing the steady-state concentration of ROS [40,41]. Therefore, although not directly investigated in this work, it is reasonable to hypothesize that also in our conditions, BSOdependent GSH depletion results in ROS production, which ultimately activates p38 MAPK /p53 signaling pathway.…”

mentioning

confidence: 77%

p38MAPK and ERK1/2 dictate cell death/survival response to different pro-oxidant stimuli via p53 and Nrf2 in neuroblastoma cells SH-SY5Y

Filomeni

Piccirillo

Rotilio

et al. 2012

Biochemical Pharmacology

View full text Add to dashboard Cite

“…Intracellular glutathione (GSH) was measured in cells seeded into 25 cm 2 tissue culture flasks (2 ϫ 10 6 cells) and treated with 500 m BSO for 24 h. Cells were then mechanically harvested with Puck's saline A + 1 mm EDTA and 10 mm Hepes, washed in PBS, centrifuged, and the pellet was acidified with 200 m 5% sulfasalicylic acid, flash frozen in liquid nitrogen vapor, and analyzed for total glutathione content within 48 h by the DTNB-GSSB reductase method, with results normalized to total protein as previously described, 17 except that the GSH assay was adapted to employ a Thermomax Microplate Reader (Molecular Devices, Sunnyvale, CA, USA).…”

Section: Measurement Of Intracellular Glutathionementioning

confidence: 99%

“…9,[12][13][14][15] We have previously reported that BSO, as a single agent, is highly cytotoxic for neuroblastoma cell lines in vitro and results in apoptosis due to increased generation of reactive oxygen species (ROS). 16,17 The combination of BSO with clinically achievable (non-myeloablative) concentrations of L-PAM was synergistic for neuroblastoma cell lines established at diagnosis or following non-myeloablative therapy. 16 Non-myeloablative trials of BSO and L-PAM in adults and children have achieved BSO levels of ෂ500 M and L-PAM levels of ෂ3 M and have shown that the combination causes reversible bone marrow suppression as the major clinical toxicity.…”

mentioning

confidence: 99%

Synergistic cytotoxicity of buthionine sulfoximine (BSO) and intensive melphalan (L-PAM) for neuroblastoma cell lines established at relapse after myeloablative therapy

Anderson

Reynolds

2002

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

Depletion of Glutathione by Buthionine Sulfoximine Is Cytotoxic for Human Neuroblastoma Cell Lines via Apoptosis

Cited by 100 publications

References 54 publications

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

p38MAPK and ERK1/2 dictate cell death/survival response to different pro-oxidant stimuli via p53 and Nrf2 in neuroblastoma cells SH-SY5Y

Synergistic cytotoxicity of buthionine sulfoximine (BSO) and intensive melphalan (L-PAM) for neuroblastoma cell lines established at relapse after myeloablative therapy

Contact Info

Product

Resources

About