SIRT1 (silent information regulator 2 homolog 1) is a crucial cellular survival
protein especially in oxidative stress environments, and has been thought to locate within the nuclei, but also known to shuttle between cytoplasm and nuclei in some cell types. Here, we show for the first time the dynamics of
SIRT1 in the presence of single or concurrent cigarette
smoke extract (CSE) exposure in human bronchial epithelial cells (HBEC). In BEAS-2B HBEC or primary HBEC,
SIRT1 was localized predominantly in cytoplasm, and the CSE (3%) induced nuclear translocation of
SIRT1 from cytoplasm in the presence of L-
buthionine sulfoximine (an irreversible inhibitor of γ-glutamylcystein
synthetase), mainly through the activation of
phosphatidylinositol 3-kinase (PI3K) α subunit. This
SIRT1 nuclear shuttling was associated with FOXO3a nuclear translocation and the strong induction of several
anti-oxidant genes including
superoxide dismutase (SOD) 2 and 3; therefore seemed to be an adaptive response. When BEAS-2B cells were pretreated with repeated exposure to a lower concentration of CSE (0.3%), the CSE-induced
SIRT1 shuttling and resultant SOD2/3
mRNA induction were significantly impaired. Thus, this result offers a useful cell model to mimic the impaired
anti-oxidant capacity in cigarette smoking-associated
lung disease such as
chronic obstructive pulmonary disease.