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Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae
Published on: April 5, 2015
Identification of new proteins related with cisplatin resistance in Saccharomyces cerevisiae
Antonio M Burgos-Molina1, Silvia Mercado-Sáenz1, Casimiro Cárdenas2
1Laboratorio de Radiobiología, Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga, Bulevar Louis Pasteur 32, 29010, Málaga, Spain.
Abstract:
The aim of this study is to select a cisplatin-resistant Saccharomyces cerevisiae strain to look for new molecular markers of resistance and the identification of mechanisms/interactions involved. A resistant strain was obtained after 80 days of cisplatin exposure. Then, total protein extraction, purification, and identification were carried out, in wild-type (wt) and resistant strains, by tandem mass spectrometry using a "nano HPLC-ESI-MS/MS" ion trap system. The increase in the exponentially modified protein abundance index (emPAI) (resistant vs wt strains) was calculated to study the increase in protein expression. "Genemania" software ( http://www.Genemania.org/ ) was used to compare the effects, functions, and protein interactions. KEGG tool was used for metabolic pathway analysis. Data are available via ProteomeXchange with identifier PXD020665. The cisplatin-resistant strain showed 2.5 times more resistance than the wt strain for the inhibitory dose 50% (ID50) value (224 μg/ml vs 89.68 μg/ml) and 2.78 times more resistant for the inhibitory dose 90% (ID90) value (735.2 μg/ml vs 264.04 μg/ml). Multiple deregulated proteins were found in the glutathione and carbon metabolism, oxidative phosphorylation, proteasome, glycolysis and gluconeogenesis, glyoxylate metabolism, fatty acid degradation pathway, citric acid cycle, and ribosome. The most overexpressed proteins in the cisplatin-resistant strain were related to growth and metabolism (QCR2, QCR1, ALDH4, ATPB, ATPA, ATPG, and PCKA), cell structure (SCW10), and thermal shock (HSP26). The results suggest that these proteins could be involved in cisplatin resistance. The resistance acquisition process is complex and involves the activation of multiple mechanisms that interact together. KEY POINTS: • Identification of new proteins/genes related to cisplatin resistance • Increased expression of QCR2/QCR1/ALDH4/ATPB/ATPA/SCW10/HSP26/ATPG and PCKA proteins • Multiple molecular mechanisms that interact together are involved in resistance.
Insights
Researchers identified new molecular markers for cisplatin resistance in Saccharomyces cerevisiae. Overexpressed proteins related to metabolism and cell structure suggest complex, interacting mechanisms contribute to resistance.
Area of Science:
- Biochemistry
- Molecular Biology
- Yeast Genetics
Background:
- Cisplatin is a widely used chemotherapy drug.
- Understanding cisplatin resistance mechanisms is crucial for improving cancer treatment.
- Saccharomyces cerevisiae serves as a model organism for studying cellular processes, including drug resistance.
Purpose of the Study:
- To select a cisplatin-resistant Saccharomyces cerevisiae strain.
- To identify novel molecular markers and understand the interactions involved in cisplatin resistance.
- To investigate the proteomic changes associated with acquired cisplatin resistance.
Main Methods:
- Exposure of wild-type Saccharomyces cerevisiae to cisplatin for 80 days to select a resistant strain.
- Proteomic analysis using nano HPLC-ESI-MS/MS for protein identification and quantification (emPAI).
- Bioinformatic analysis with GeneMANIA for protein interactions and KEGG for metabolic pathways.
Main Results:
- The resistant strain exhibited significantly higher resistance to cisplatin (ID50 and ID90 values).
- Proteomic analysis revealed deregulation in multiple metabolic pathways, including glutathione metabolism, oxidative phosphorylation, and glycolysis.
- Overexpression of specific proteins involved in growth, metabolism (e.g., QCR2, ALDH4, ATPB), cell structure (SCW10), and thermal shock (HSP26) was observed.
Conclusions:
- The identified overexpressed proteins (QCR2, QCR1, ALDH4, ATPB, ATPA, ATPG, PCKA, SCW10, HSP26) are potential molecular markers for cisplatin resistance.
- Cisplatin resistance in Saccharomyces cerevisiae is a complex trait involving the interplay of multiple molecular mechanisms.
- Further research into these proteins and pathways could lead to strategies to overcome cisplatin resistance in cancer therapy.
