Aspartate facilitates mitochondrial function, growth arrest and survival during doxorubicin exposure

Cell Cycle
Ken DornfeldKendall B Wallace

Abstract

Genomic screens of doxorubicin toxicity in S. cerevisiae have identified numerous mutants in amino acid and carbon metabolism which express increased doxorubicin sensitivity. This work examines the effect of amino acid metabolism on doxorubicin toxicity. S. cerevisiae were treated with doxorubicin in combination with a variety of amino acid supplements. Strains of S. cerevisiae with mutations in pathways utilizing aspartate and other metabolites were examined for sensitivity to doxorubicin. S. cerevisiae cultures exposed to doxorubicin in minimal media showed significantly more toxicity than cultures exposed in rich media. Supplementing minimal media with aspartate, glutamate or alanine reduced doxorubicin toxicity. Cell cycle response was assessed by examining the budding pattern of treated cells. Cultures exposed to doxorubicin in minimal media arrested growth with no apparent cell cycle progression. Aspartate supplementation allowed cultures exposed to doxorubicin in minimal media to arrest after one division with a budding pattern and survival comparable to cultures exposed in rich media. Aspartate provides less protection from doxorubicin in cells mutant in either mitochondrial citrate synthase (CIT1) or NADH oxidase (NDI1...Continue Reading

References

May 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S DiNardoR Sternglanz
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·S A Jelinsky, L D Samson
Dec 5, 2000·Molecular Biology of the Cell·A P GaschP O Brown
Jan 15, 2003·The Journal of Biological Chemistry·Eva AlbersLena Gustafsson
Sep 13, 2003·Pharmacology & Toxicology·Kendall B Wallace
Jan 1, 1960·Proceedings of the Society for Experimental Biology and Medicine·G A FLEISHERK G WAKIM
Nov 30, 2005·Nucleic Acids Research·Ken Dornfeld, Monika Johnson
Apr 21, 2007·Methods in Cell Biology·Ann Saada Reisch, Orly Elpeleg
Jul 4, 2007·Proceedings of the National Academy of Sciences of the United States of America·John L Hartman
Sep 29, 2007·Cardiovascular Toxicology·Jessica M Berthiaume, Kendall B Wallace
Oct 14, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Aaron K OlsonMichael A Portman
Jan 8, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Malgorzata Tokarska-SchlattnerUwe Schlattner
Feb 6, 2010·Toxicology·Rui A CarvalhoKendall B Wallace
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Mar 15, 2011·Cardiovascular Research·Christine Des RosiersJohn C Chatham
Jan 6, 2012·Genetics·Audrey S Howell, Daniel J Lew
Mar 16, 2012·Genetics·Per O Ljungdahl, Bertrand Daignan-Fornier
Jul 4, 2012·Current Heart Failure Reports·Carrie GeisbergDouglas B Sawyer
Jun 19, 2014·Genetics·Guri Giaever, Corey Nislow

❮ Previous
Next ❯

Citations

Feb 2, 2019·Frontiers in Endocrinology·Oana PînzariuCarmen E Georgescu
Sep 14, 2018·Scientific Reports·Hilal Taymaz-NikerelBetül Kırdar
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mei HanTao Su

❮ Previous
Next ❯

Methods Mentioned

BETA
deamination

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.