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Global effects of adriamycin treatment on mouse splenic protein levels
Adam R Evans1, Sumitra Miriyala, Daret K St Clair
1Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Abstract:
Adriamycin (ADR) is a potent anticancer drug used to treat a variety of cancers. Patients treated with ADR have experienced side effects such as heart failure, cardiomyopathy, and "chemobrain", which have been correlated to changes in protein expression in the heart and brain. In order to better understand cellular responses that are disrupted following ADR treatment in immune tissues, this work focuses on spleen. Significantly reduced spleen sizes were found in ADR-treated mice. Global isotopic labeling of tryptic peptides and nanoflow reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) were employed to determine differences in the relative abundances of proteins from ADR-treated mice relative to controls. Fifty-nine proteins of the 388 unique proteins identified showed statistically significant differences in expression levels following acute ADR treatment. Differentially expressed proteins are involved in processes such as cytoskeletal structural integrity, cellular signaling and transport, transcription and translation, immune response, and Ca(2+) binding. These are the first studies to provide insight to the downstream effects of ADR treatment in a peripheral immune organ such as spleen using proteomics.
Insights
Adriamycin (ADR) treatment significantly impacts spleen size and protein expression. Proteomics reveals altered proteins involved in immune response and cellular functions, offering new insights into ADR
Area of Science:
- Proteomics
- Immunology
- Pharmacology
Background:
- Adriamycin (ADR) is a chemotherapy drug with known cardiotoxic and neurotoxic side effects.
- These side effects are linked to altered protein expression in the heart and brain.
- The impact of ADR on peripheral immune organs like the spleen remains largely uncharacterized.
Purpose of the Study:
- To investigate the proteomic changes in the spleen following Adriamycin (ADR) treatment.
- To understand the cellular responses disrupted in immune tissues by ADR.
- To identify specific proteins and pathways affected by ADR in the spleen.
Main Methods:
- Utilized global isotopic labeling of tryptic peptides for quantitative proteomics.
- Employed nanoflow reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) for protein identification and quantification.
- Analyzed spleens from ADR-treated and control mice.
Main Results:
- ADR treatment led to a significant reduction in spleen size.
- Identified 388 unique proteins, with 59 showing statistically significant differential expression.
- Affected proteins are involved in cytoskeletal integrity, cellular signaling, transport, transcription, translation, immune response, and calcium ion (Ca2+) binding.
Conclusions:
- ADR significantly alters protein expression profiles in the spleen, a key peripheral immune organ.
- These proteomic changes suggest disruptions in fundamental cellular processes and immune functions.
- This study provides novel insights into the downstream effects of ADR treatment on immune tissues.