Cytotoxicity of Oleandrin Is Mediated by Calcium Influx and by Increased Manganese Uptake in Saccharomyces cerevisiae Cells.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Lavinia L RutaIleana C Farcasanu

Abstract

Oleandrin, the main component of Nerium oleander L. extracts, is a cardiotoxic glycoside with multiple pharmacological implications, having potential anti-tumoral and antiviral characteristics. Although it is accepted that the main mechanism of oleandrin action is the inhibition of Na+/K+-ATPases and subsequent increase in cell calcium, many aspects which determine oleandrin cytotoxicity remain elusive. In this study, we used the model Saccharomyces cerevisiae to unravel new elements accounting for oleandrin toxicity. Using cells expressing the Ca2+-sensitive photoprotein aequorin, we found that oleandrin exposure resulted in Ca2+ influx into the cytosol and that failing to pump Ca2+ from the cytosol to the vacuole increased oleandrin toxicity. We also found that oleandrin exposure induced Mn2+ accumulation by yeast cells via the plasma membrane Smf1 and that mutants with defects in Mn2+ homeostasis are oleandrin-hypersensitive. Our data suggest that combining oleandrin with agents which alter Ca2+ or Mn2+ uptake may be a way of controlling oleandrin toxicity.

References

Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J Nakajima-ShimadaY Anraku
Mar 1, 1995·Molecular and Cellular Biology·P J LapinskasV C Culotta
May 3, 1996·Toxicology·S D Langford, P J Boor
Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·H Zhao, D Eide
May 14, 1996·Proceedings of the National Academy of Sciences of the United States of America·F SupekN Nelson
Sep 20, 1996·The Journal of Biological Chemistry·H Zhao, D Eide
Sep 20, 1996·The Journal of Biological Chemistry·A F BatizaP H Masson
Aug 26, 1998·Annual Review of Nutrition·D J Eide
Feb 13, 1999·The Journal of Biological Chemistry·J LeeM B Toledano
Jan 15, 2000·Bioscience, Biotechnology, and Biochemistry·I C FarcasanuT Miyakawa
Jun 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·C P PalmerY Saimi
Jan 10, 2002·The Journal of Cell Biology·Valerie Denis, Martha S Cyert
Jun 21, 2002·Methods in Enzymology·Fred Sherman
Jul 27, 2002·Annual Review of Microbiology·Anthony Van HoJerry Kaplan
Aug 19, 2003·The Journal of Biological Chemistry·Laran T JensenValeria Cizewski Culotta
Feb 6, 2004·Journal of Biochemistry and Molecular Biology·Juan I Castrillo, Stephen G Oliver
Aug 10, 2004·The Journal of Biological Chemistry·Laia ViladevallJoaquín Ariño
Jul 9, 2005·Eukaryotic Cell·Valeria Cizewski CulottaMatthew D Hall
Dec 27, 2005·Bioscience, Biotechnology, and Biochemistry·Ileana Cornelia FarcasanuTokichi Miyakawa
Jan 12, 2007·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·P CourvilleM F M Cellier
Jun 21, 2008·Neurotoxicology·Catherine AuMichael Aschner
Mar 8, 2011·Cell Calcium·Kyle W Cunningham
Aug 2, 2012·Cancer Chemotherapy and Pharmacology·Renata MatuoJoão Antonio Pêgas Henriques
Mar 31, 2015·Current Opinion in Biotechnology·Sandra C dos Santos, Isabel Sá-Correia
Jun 1, 2017·Journal of Ethnopharmacology·Ana Flávia Machado BotelhoMarília Martins Melo
Jun 4, 2017·Applied Microbiology and Biotechnology·Lavinia Liliana RutaIleana Cornelia Farcasanu
Dec 27, 2017·Anticancer Research·Bodil HernrothHelena Tassidis

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic

Software Mentioned

Prism
GraphPad

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.

Related Papers

Journal of the American College of Emergency Physicians Open
Robert A Newman, K Jagannadha Sastry
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Stefano GarofaloCristina Limatola
Archives Internationales De Pharmacodynamie Et De Thérapie
S I DeaversJ D McCrady
© 2022 Meta ULC. All rights reserved