Redox Proteomics of Oxidative Stress-Induced Cell Death Haiteng Deng.

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Presentation transcript:

Redox Proteomics of Oxidative Stress-Induced Cell Death Haiteng Deng

Effects of Oxidative Stress on Carcinogenesis and Cancer Treatment Chronic Oxidative Stress inflammation genetic disorder environment Tumor Formation Genetic instability New phenotypes Apoptosis Growth Etc. Carcinogenesis Cancer Treatment ROS-based Therapy Induced apoptosis or Necrosis Tumor Regression Oxidative resistant cells NO YES Anti-Cancer Agents Doxorubicin Daunorubicin Mitomycin C Etoposide Cisplatin Arsenic trioxide Ionizing radiation

Azacitidine Action Mechansims of Two Drugs

(c) MarkerAzacytidine Control (b) (a) Azacytidine/Gossypol Induced Cell Type-Specific Cell Death: Apoptosis, Necrosis and Autophagy Percentage of apoptosis-related cell death by FACS analsis

Human Albumin Y—I—C—E—N—Q—D—S—I—S—S--K Azacytidine Induced Changes of Protein Expressions

Azacytidine/Gossypol/H 2 O 2 Induced Similar Changes of Protein Expressions

Control Gossypol treated Detection of Reactive Oxygen Species by Fluorescein Labeling

Trachootham et al., Naturee Review Drug Discovery 8 (2009) 579 Effects of ROS on Cellular Processes

Metabolomics Analysis of Gossypol-treated Ovarian Cancer Cells

Redox Proteomics Analysis of Gossypol-treated Cells Leichert et al., PNAS 2008, 105, p8199

 120 unique ICAT-modified peptides with an ion-score of 95% or higher with cICAT  1723 carboxymethylated peptides  Changes of 545 cysteine-containing peptides from 356 proteins  Quantitatio is quite time-consuming Redox Proteomics Analysis of Gossypol-treated Cells

Functional Classification of Differentially Regulated Proteins with PANTHER

The Occurring Frequency of Amino Acids Immediately Before or After the Cysteine Residue

Changes of Redox States of Specific Cysteine Residues

Changes of Redox States of HSP60

HSP90 HSP70 HSP60 ？ Complexes of Flag-tagged HSP60 in 293T Cells Under Reducing and Non-Reducing Conditions

Dimitrios Anastasiou et al. Science 334, 1278 (2011);

Effects of ROS on Warburg Effect

Challenges in Redox Biology ROS Production and Localization Signal Transduction Characterization of Low Abundance Regulatory Proteins

Pr-Cys-SH Pr-Cys-SOH Pr-Cys-SO 2 H Pr-Cys-SO 3 H Pr-Cys-S-SG ROS Pr-Cys-SNO 214,000 Cysteine Residues in Human Proteome with Different Oxidations Physiological Pathological Reversible Signaling Irreversible Damage

22 Tang, Haiping Chen, Yuling Wang, Jia Miao Di Liu, Jieyuan Gao, Yan Xie, Yuping Zou, Haijie Acknowledgments