Lanthanum chloride suppresses oxysterol-induced ECV-304 cell apoptosis via inhibition of intracellular Ca(2+) concentration elevation, oxidative stress, and activation of ERK and NF-κB signaling pathways.

Abstract

Experimental studies have demonstrated that oral administration of lanthanum chloride (LaCl(3)) inhibits the development of atherosclerosis, but the related mechanism has not been fully elucidated. Oxysterols are toxic to the vascular endothelial cells which are important in preventing the formation and progression of atheromatous plaque. In this study, we examined the effect of LaCl(3) on oxysterol cholestane-3β,5α,6β-triol (Triol)-induced apoptosis and the related mechanisms in ECV-304 cells, a presumptive endothelial cell line. Incubation with Triol resulted in apoptosis of ECV-304 cells, as determined by Hoechst 33342 staining, fluorescein isothiocyanate labeled annexin V/propidium iodide double staining, and the loss of mitochondrial membrane potential. Triol activated extracellular-signal-regulated kinase (ERK) and nuclear factor κB (NF-κB), and inhibition of Triol-activated ERK and NF-κB signaling by specific inhibitors attenuated apoptosis induction by Triol in ECV-304 cells. Pretreatment with LaCl(3) (1 μM) for 12 h before exposure to Triol decreased Triol-mediated apoptosis as well as activation of ERK and NF-κB. In addition, Triol induced oxidative stress in ECV-304 cells, manifested by the increase of intracellular reactive oxygen species generation and malondialdehyde level, and the reduction of the content of total protein thiols and the activity of antioxidant glutathione peroxidases; LaCl(3) pretreatment significantly reversed these effects. Finally, LaCl(3) pretreatment significantly inhibited the increases of intracellular Ca(2+) concentration induced by Triol. Our study suggests that Triol induced ECV-304 cell apoptosis, and LaCl(3) could suppress this effect probably by inhibiting intracellular Ca(2+) concentration elevation, oxidative stress, as well as activation of ERK and NF-κB signaling pathways.

• Authors: Hongmei Liu, Congcong Zhang, Kaixun Huang
• Journal: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry (J Biol Inorg Chem) Vol. 16 Issue 5 Pg. 671-81 (Jun 2011) ISSN: 1432-1327 [Electronic] Germany
• PMID: 21359969 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Sulfhydryl Compounds
• lanthanum chloride
• Lanthanum
• Extracellular Signal-Regulated MAP Kinases
• Calcium

Topics

• Apoptosis (drug effects)
• Calcium (metabolism)
• Cell Line
• Endothelial Cells (cytology, drug effects, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Lanthanum (pharmacology)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Signal Transduction (drug effects)
• Sulfhydryl Compounds (pharmacology)