Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes.
The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca2+ on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca2+ pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca2+ entrance was induced by A23187 in HepG2. Cell death, Ca2+ mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca2+ concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and l-NAME enhanced, GCDCA-induced cell death. The reduction of Ca2+ entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca2+ entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca2+ concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca2+-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.
González-Rubio
Sandra
S
Liver Research Unit, Reina Sofía University Hospital, Córdoba, Spain.
Linares
Clara I
CI
Bello
Rosario I
RI
González
Raul
R
Ferrín
Gustavo
G
Hidalgo
Ana B
AB
Muñoz-Gomariz
Elisa
E
Rodríguez
Blanca A
BA
Barrera
Pilar
P
Ranchal
Isidora
I
Durán-Prado
Mario
M
Aguilar-Melero
Patricia
P
De la Mata
Manuel
M
Muntané
Jordi
J
D000111:Acetylcysteine / Q000494:pharmacology*; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D005999:Glycochenodeoxycholic Acid / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D009838:Oligodeoxyribonucleotides
D009838:Oligodeoxyribonucleotides; D009569:Nitric Oxide; D005999:Glycochenodeoxycholic Acid; D002118:Calcium; D000111:Acetylcysteine