Adaptation to acrolein through upregulating the protection by glutathione in human bronchial epithelial cells: The materialization of the hormesis concept

作者：Sthijns Mireille M J P E^*; Randall Matthew J; Bast Aalt; Haenen Guido R M M

来源：Biochemical and Biophysical Research Communications, 2014, 446(4): 1029-1034.

DOI：10.1016/j.bbrc.2014.03.081

• Acrolein
• GSH
• gamma GCS
• Human bronchial epithelial cells
• Hormesis

Acrolein is a thiol reactive compound present in cigarette smoke and plays a pivotal role in the deleterious effects of smoking. Acrolein causes toxicity in human bronchial epithelial cells in a dose dependent manner. GSH forms the first line of defense against acrolein-induced toxicity. At high doses of acrolein (%26gt;= 10 mu M) the capacity of the cellular protection by GSH is overwhelmed and GSH is not able to quench all the acrolein, resulting in cytotoxicity. At a relatively low dose of acrolein (3 mu M), no cytotoxicity is observed due to protection by GSH. Moreover we found that exposure to a low dose of acrolein protects cells against the toxic effect of a second higher dose of acrolein. The adaptation to acrolein is induced via Nrf2 mediated gene expression of gamma-glutamylcysteine synthetase leading to elevated GSH levels. This upregulation of the protection by GSH demonstrates a hormetic response to acrolein. Hormesis is an adaptive or compensatory response induced by a relatively subtle challenge of homeostasis by a toxic compound. Insight into the mechanism of hormesis is mandatory for a more accurate societal regulation of toxic compounds.

• 出版日期2014-4-18