Get access

Impact of dihydrolipoic acid on mouse embryonic stem cells and related regulatory mechanisms

Authors

  • Wen-Hsiung Chan,

    1. Department of Bioscience Technology, Chung Yuan Christian University, Chung Li 32023, Taiwan
    2. Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan
    Search for more papers by this author
  • Wei-Li Houng,

    1. Department of Bioscience Technology, Chung Yuan Christian University, Chung Li 32023, Taiwan
    2. Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan
    Search for more papers by this author
  • Cheng-An J. Lin,

    1. Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    2. Center for Nano Bioengineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    Search for more papers by this author
  • Chih-Hsien Lee,

    1. Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    2. Center for Nano Bioengineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    Search for more papers by this author
  • Po-Wen Li,

    1. Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    2. Center for Nano Bioengineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    Search for more papers by this author
  • Jyun-Tai Hsieh,

    1. Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    2. Center for Nano Bioengineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    Search for more papers by this author
  • Ji-Lin Shen,

    1. Department of Physics, Chung Yuan Christian University, Chung Li 32023, Taiwan
    Search for more papers by this author
  • Hung-I Yeh,

    1. Cardiac Medicine, Mackay Memorial Hospital, Taipei, Taiwan
    Search for more papers by this author
  • Walter H. Chang

    Corresponding author
    1. Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    2. Center for Nano Bioengineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    • Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li 32023, Taiwan
    Search for more papers by this author

Abstract

α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). Recently, DHLA has been used as the hydrophilic nanomaterial preparations, and therefore, determination of its bio-safety profile is essential. In this article, we show that DHLA (50–100 μM) induces apoptotic processes in mouse embryonic stem cells (ESC-B5), but exerts no injury effects at treatment dosages below 50 μM. Higher concentrations of DHLA (50–100 μM) directly increased the reactive oxygen species (ROS) content in ESC-B5 cells, along with a significant increase in cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases-9 and −3, and cell death. Pretreatment with NO scavengers suppressed the apoptotic biochemical changes induced by 100 μM DHLA and promoted the gene expression levels of p53 and p21 involved in apoptotic signaling. Our results collectively indicate that DHLA at concentrations of 50–100 μM triggers apoptosis of ESC-B5 cells, which involves both ROS and NO. Importantly, at doses of less than 50 μM (0–25 μM), DHLA does not exert hazardous effects on ESC-B5 cell properties, including viability, development and differentiation. These results provide important information in terms of dosage safety and biocompatibility of DHLA to facilitate its further use as a precursor for biomaterial preparation. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Ancillary