چکیده (انگلیسی):

Cigarette smoke (CS) is a major risk factor for emphysematous changes in the lungs and the
underlying mechanism involves CS-induced cell death. In the present study we investigated
the ability of nutrients to rescue CS-induced cell death. We observed that pre-treatment
with excess leucine can partially rescue CS extract-induced cell death in Saccharomyces
cerevisiae and alveolar epithelial A549 cells. Excess dietary leucine was also effective in
alleviating effects of CS in guinea pig lungs. Further investigation to understand the underlying
mechanism showed that CS exposure causes downregulation of leucine transporter
that results in inactivation of mTOR, which is a positive regulator of protein synthesis and
cell proliferation. Notably, leucine supplemented diet ameliorated even existing CS-induced
emphysematous changes in guinea pig lung, a condition hitherto thought to be irreversible.
Thus the current study documents a new mechanism by which CS affects cellular physiology
wherein leucine transporter is a key target.