Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

Journal Article · Fri Jan 15 00:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.10.003· OSTI ID:21344837

Gonzalez-Rubio, Sandra; Linares, Clara I; Bello, Rosario I ^[1]; Gonzalez, Raul; Ferrin, Gustavo ^[1]; Hidalgo, Ana B ^[1]; Munoz-Gomariz, Elisa ^[2]; Rodriguez, Blanca A ^[1]; Barrera, Pilar; Ranchal, Isidora ^[1]; Duran-Prado, Mario ^[3]; Aguilar-Melero, Patricia ^[1]; De la Mata, Manuel ^[1]; Muntane, Jordi ^[1]

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1. Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain)
2. Department of Biostatistics, Reina Sofia University Hospital, Cordoba (Spain)
3. Instituto de Parasitologia y Biomedicina Lopez Neyra, CSIC, Granada (Spain)

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 Ca{sup 2+} on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca{sup 2+} 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 Ca{sup 2+} entrance was induced by A23187 in HepG2. Cell death, Ca{sup 2+} mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca{sup 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{sup 2+} entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca{sup 2+} 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 Ca{sup 2+} concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca{sup 2+}-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

• OSTI ID: 21344837
• Journal Information: Toxicology and Applied Pharmacology, Vol. 242, Issue 2; Other Information: DOI: 10.1016/j.taap.2009.10.003; PII: S0041-008X(09)00425-6; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BILE ACIDS
CALCIUM IONS
EGTA
GLUTATHIONE
LIVER CELLS
NITRIC OXIDE
OXIDATION
STIMULATION
STRESSES
ALCOHOLS
ANIMAL CELLS
CARBOXYLIC ACIDS
CHALCOGENIDES
CHARGED PARTICLES
CHELATING AGENTS
CHEMICAL REACTIONS
DRUGS
GLYCOLS
HYDROXY COMPOUNDS
IONS
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
SOMATIC CELLS
STEROIDS
STEROLS