Ai
rway epithelium is a p
rincipal ta
rget fo
r inhaled oxidants like ciga
rette smoke, which induce epithelial inju
ry and the
reby p
rovoke pathogenesis of ch
ronic ai
rway diseases. Alte
rations in ai
rway epithelial glutathione (GSH) metabolism a
re cent
ral in causing a loss of
reducing envi
ronment, howeve
r, data a
re sca
rce on epithelial cells f
rom la
rge
r b
ronchi. We showed a t
ransient depletion of int
racellula
r GSH in human b
ronchial epithelial cells afte
r exposu
re to ciga
rette smoke condensate (CSC), which late
r followed by a p
rolonged elevation. Of the GSH-
regulating enzymes, CSC inc
reased mRNA exp
ression of both catalytic (GCLC) and modifie
r (GCLM) subunits of glutamate-cysteine ligase. UPF1, a tet
rapeptide GSH analogue, 4-methoxy-l-ty
rosinyl-¦Ã-l-glutamyl-l-cysteinyl-glycine, known to possess a 50-fold highe
r hyd
roxyl
radical scavenging efficiency than does GSH, no
rmalized the int
racellula
r GSH level in the human b
ronchial epithelial cells unde
r oxidative st
ress caused by CSC. UPF1
resto
red the GCLM and GSH
reductase mRNA levels, which we
re significantly augmented by CSC t
reatment, back to the level of unt
reated cont
rol cells,
refe
rring to a successful establishment of cont
rol by UPF1 upon the ove
r-accumulation of GSH. Mo
reove
r, UPF1 showed a significantly mo
re potent antioxidant capacity than did N-acetyl-l-cysteine (NAC) and, compa
red to NAC, demonst
rated a bette
r potential to assu
re the whole GSH homeostasis in human b
ronchial epithelial cells.
The current study suggests that UPF1 is capable of maintaining intracellular GSH level under CSC-induced oxidative stress in bronchial epithelial cells via balanced control over GSH-regulating enzymes, reflecting an improved perception of cellular redox conditions and thereby warranting improved adjustment of GSH accumulation.