Induction of Fas receptor and Fas ligand by nodularin is mediated by NF-{kappa}B in HepG2 cells

Journal Article · Tue Mar 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.01.009· OSTI ID:21535255

Ying, Li; Yansheng, Bai ^[1]

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1. Anong Biotech Institute, Tianjin (China)

Nodularin is a natural toxin with multiple features, including inhibitor of protein phosphatases 1 and 2A as well as tumor initiator and promoter. One unique feature of nodularin is that this chemical is a hepatotoxin. It can accumulate into the liver after contact and lead to severe damage to hepatocyte, such as apoptosis. Fas receptor (Fas) and Fas ligand (FasL) system is a critical signaling network triggering apoptosis. In current study, we investigated whether nodularin can induce Fas and FasL expression in HepG2 cell, a well used in vitro model for the study of human hepatocytes. Our data showed nodularin induced Fas and FasL expression, at both mRNA and protein level, in a time- and dose-dependent manner. We also found nodularin induced apoptosis at the concentration and incubation time that Fas and FasL were significantly induced. Neutralizing antibody to FasL reduced nodularin-induced apoptosis. Further studies demonstrated that nodularin promoted nuclear translocation and activation of p65 subunit of NF-{kappa}B. By applying siRNA targeting p65, which knocked down p65 in HepG2 cells, we successfully impaired the activation of NF-{kappa}B by nodularin. In these p65 knockdown cells, we observed that Fas and FasL expression and apoptosis induced by nodularin were significantly reduced. These findings suggest the induction of Fas and FasL expression and thus cell apoptosis in HepG2 cells by nodularin is mediated through NF-{kappa}B pathway.

• OSTI ID: 21535255
• Journal Information: Toxicology and Applied Pharmacology, Vol. 251, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.01.009; PII: S0041-008X(11)00018-4; Copyright (c) 2011 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
ANTIBODIES
APOPTOSIS
DAMAGE
DOSES
HUMAN POPULATIONS
IN VITRO
INCUBATION
LIGANDS
LIVER
LIVER CELLS
MESSENGER-RNA
NEOPLASMS
PHOSPHATASES
RECEPTORS
TOXINS
ANIMAL CELLS
ANTIGENS
BODY
DIGESTIVE SYSTEM
DISEASES
ENZYMES
ESTERASES
GLANDS
HAZARDOUS MATERIALS
HYDROLASES
MATERIALS
MEMBRANE PROTEINS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POPULATIONS
PROTEINS
RNA
SOMATIC CELLS
TOXIC MATERIALS