Heat shock protein induction protects human respiratory epithelium against nitric oxide-mediated cytotoxicity.
Induction of heat shock proteins (HSPs) confers protection against a variety of cytotoxic agents. We hypothesized that induction of HSPs would protect cultured human respiratory epithelium against nitric oxide (NO)-mediated injury. Incubation of a human bronchial epithelial cell line (BEAS-2B cells) at 43 degrees C for 1.5 h induced expression of several HSPs. Prior induction of HSPs was associated with protection against the NO-donors S-nitroso-N-acetyl penicillamine and 3-morpholinsydnonimine. Protection was evident as improved short term survival and improved ability of cells to recover and proliferate after exposure to NO. Prior induction of HSPs also attenuated NO-mediated decreases in cellular ATP levels, but did not decrease nitrotyrosine formation. Specific overexpression of HSP-70 by plasmid-directed gene transfer protected murine respiratory epithelial cells against S-nitroso-N-acetyl penicillamine. We conclude that in cultured human respiratory epithelium induction of HSPs confers protection against NO-mediated cytotoxicity, possibly by preservation of cellular energetics. We also suggest that HSP-70 may play a specific role in protection.
Wong
H R
HR
Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, OH 45229, USA. wonghr@chmcc.org
Ryan
M
M
Menendez
I Y
IY
Denenberg
A
A
Wispé
J R
JR
D000255:Adenosine Triphosphate / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism*; D018869:Heat-Shock Response; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000255:Adenosine Triphosphate