Interaction of aryl hydrocarbon receptor-mediated apoptosis of neuronal cells with estrogen receptor signaling

• Autorzy: Kajta M. , Wojtowicz A.K. , Mackowiak M. , Lason W.
• Języki publikacji: EN

Abstrakty

EN

Aryl hydrocarbon receptor (AhR) may be responsible for dioxin intoxication, which creates severe clinical problems, such as behavioural and cognitive impairments and an increased number of newborns with deformed brains. Thus, activation of AhRs induces neuronal damage, but the mechanism by which this occurs is largely unknown. Because beta-naphthofl avone is an AhR agonist, we evaluated its impact on apoptotic processes in the mouse primary neuronal cell cultures. In order to verify whether AhR-mediated activation of caspase-3 and lactate dehydrogenase (LDH) release were tissue- and age-dependent, we related them to neocortical and hippocampal tissues, both on 1 and 7 days in vitro. In addition to the effects of estrogen receptor (ER) antagonists and selective estrogen receptor modulators (SERMs), the interaction between AhR-induced apoptosis and ER signaling was evaluated by determining the levels and cellular distribution of AhR and ERbeta. beta-naphtofl avone (0.1ñ100 mM) enhanced caspase-3 activity and LDH release in neocortical and hippocampal cells. A high-affi nity ER antagonist, ICI 182,780, and SERM, tamoxifen, enhanced beta-naphtofl avone-mediated apoptosis. Another SERM, raloxifene, and an ERalpha antagonist, methylpiperidino-pyrazole, did not affect beta-naphtofl avone-induced caspase-3 activity. However, they inhibited beta-naphtofl avoneinduced LDH release at late hour post-treatment, thus suggesting delayed control of AhR-mediated neuronal cell death. The apoptotic effects of beta-naphtofl avone were accompanied by increased levels of AhRs, and these receptors colocalized with ERbeta as demonstrated by confocal microscopy. These data provide evidence for direct interaction of the AhR-mediated apoptotic pathway with estrogen receptor signaling, which gives insight into new strategies to treat or prevent AhR-mediated neurotoxicity. This work was supported by the Polish Ministry of Education and Science, grant No. 2P05A 123 30, and also by the Institute of Pharmacology of Polish Academy of Sciences statutory funds.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.97

Twórcy

autor

Kajta M.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Wojtowicz A.K.

• Laboratory of Physiology and Toxicology of Reproduction, Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland

autor

Mackowiak M.

• Department of Pharmacology, Laboratory of Brain Pharmacology and Biostructure, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Lason W.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland