Thymosin β4 cytoplasmic/nuclear translocation as a new marker of cellular stress. A Caco2 case study

Biomarkers of cell stress are important for proper diagnosis, and in studies of how cells respond to drug treatment. Biomarkers that respond early to pharmacological treatment could improve therapy by tailoring the treatment to the needs of the patient. Thymosin beta-4 (Tβ₄) plays a significant role in many aspects of cellular metabolism because of its actin-sequestering properties. Other physiological functions of Tβ₄ have been also reported. Among these, Tβ₄ may play a crucial role during cellular stress. We addressed the relevance of Tβ₄ in cellular stress conditions by using different treatments (serum starvation, DMSO, and butyrate administration) in a colon adenocarcinoma cell line (CaCo2), a cell line frequently used for in vitro experimental studies of Tβ₄. In this study, different stress stimuli were analyzed and the obtained results were compared using immunocytochemistry, and molecular and biochemical methods. Taken together, the data clearly indicate that the Tβ₄ peptide is involved in adaptive and defensive cellular mechanisms, and that different stress inducers lead to a similar Tβ₄ cytoplasmic/nuclear translocation. The translocation of Tβ₄ between the cytoplasm and the nucleus of the cell seems characteristic of a possible molecular response to cellular stress exerted by this peptide.