12-o-retinoylphorbol-13-acetate and Starvation

We induced upregulation of stanniocalcin-1 (STC-1) by various mild and long lasting stresses and assayed its influence on mitochondrial membrane potential (MMP) in the neural crest-derived cell line Paju. The obtained data showed that starvation (24-96 h), exposure to 10nM TPA, and low concentrations (0.05-1 μM) of As2O3 significantly (3-5 times) upregulated Paju cell STC-1 RNA and stabilized the mitochondrial membrane potential (MMP). However, high concentrations of As2O3 (2.5-5.0 μM) increased intracellular ROS and free calcium levels and, consequently, suppressed STC-1 and MMP. The results show that cells preconditioned by various mild stresses expressed more STC-1 and their MMP were more resistant to a secondary exposure to As2O3 (2.5-5 μM, 96 h) demonstrating mitohormesis. We suggest that MMP deviation from control levels, to an extent innocuous to cell viability, is a general signal for STC-1-induction and MMP-protection. Our findings of Paju cell MMP-regulation may be of great importance for inventing new ways to prevent neurodegenerative diseases and unravel the mechanisms behind drug resistance.

Topics: Adrenal Gland Neoplasms; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Calcium; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Flow Cytometry; Glycoproteins; Hormesis; Humans; Membrane Potential, Mitochondrial; Mitochondria; Neuroblastoma; Oxides; Phorbol Esters; Reactive Oxygen Species; Starvation; Stress, Physiological; Time Factors; Up-Regulation