Mitochondrial-driven ubiquinone enhances extracellular calcium-dependent nitric oxide production and reduces glycochenodeoxycholic acid-induced cell death in hepatocytes.
Ca(2+) mobilization, nitric oxide (NO), and oxidative stress have been involved in cell death induced by hydrophobic bile acid in hepatocytes. The aim of the study was the elucidation of the effect of the antioxidant mitochondrial-driven ubiquinone (Mito Q) on the intracellular Ca(2+) concentration, NO production, and cell death in glycochenodeoxycholic acid (GCDCA)-treated HepG2 cells. The role of the regulation of the intracellular Ca(2+) concentration by Ca(2+) chelators (EGTA or BAPTA-AM), agonist of Ca(2+) entrance (A23187) or NO (L-NAME or NO donor), was assessed during Mito Q cytoprotection in GCDCA-treated HepG2 cells. Cell death, NO synthase (NOS)-1, -2, and -3 expression, Ca(2+) mobilization, and NO production were evaluated. GCDCA reduced the intracellular Ca(2+) 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 Ca(2+) entry by EGTA, but not its release from intracellular stores by BAPTA-AM, reduced the expression of NOS-3 and enhanced cell death in control and GCDCA-treated cells. Mito Q prevented the reduction of intracellular Ca(2+) concentration, NOS-3 expression, NO production, and cell death in GCDCA-treated HepG2 cells. The conclusion is that the recovery of Ca(2+)-dependent NOS-3 expression by Mito Q may be considered an additional cytoprotective property of an antioxidant.
González-Rubio
Sandra
S
Liver Research Unit, Reina Sofia University Hospital, Cordoba, Spain.
Hidalgo
Ana B
AB
Ferrín
Gustavo
G
Bello
Rosario I
RI
González
Raul
R
Gahete
Manuel D
MD
Ranchal
Isidora
I
Rodríguez
Blanca A
BA
Barrera
Pilar
P
Aguilar-Melero
Patricia
P
Linares
Clara I
CI
Castaño
Justo P
JP
Victor
Victor M
VM
De la Mata
Manuel
M
Muntané
Jordi
J
D017209:Apoptosis / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D005999:Glycochenodeoxycholic Acid / Q000737:chemistry* / Q000633:toxicity; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism*
D014451:Ubiquinone; D009569:Nitric Oxide; D000001:Calcimycin; D005999:Glycochenodeoxycholic Acid; D052250:Nitric Oxide Synthase Type III; D053148:Caspase 3; D002118:Calcium