Endoplasmic reticulum protein ERp29 and doxorubicininduced toxicity in H9c2 cardiomyocytes: a comparative proteomics analysis

Background: Doxorubicin has been widely used to treat many cancers. It also induces cumulative and delayed cardiomyopathy. New biological markers to predict cardiac toxicity is needed.

Objectives: We identified novel markers and potential therapeutic targets of doxorubicin (DOX)-induced cardiac toxicity by proteomics approach.

Methods: The protein profiling of H9c2 cells in response to DOX at an apoptosis-induced concentration (0.5⃞M) were compared by two-dimensional electrophoresis (2-DE) and mass spectrometry.

Results: A total of nine differently expressed proteins were identified including six up-regulated and three downregulated proteins. We further confirmed the expression of two down-regulated proteins, prohibitin and endoplasmic reticulum protein ERp29 (ERp29), decreased in response to DOX induction by Western-blot, and over-expression of ERp29 also partially recovered the MTT reduction.

Conclusion: We first identified ERp29 and prohibitin as novel markers for DOX toxicity, and ERp29 might be a candidate target to develop novel therapeutic strategies to alleviate adverse effects of doxorubicin-based chemotherapies.