Zinc-induced inhibition of protein synthesis and reduction of connexin-43 expression and intercellular communication in mouse cortical astrocytes.
Zinc released from a subpopulation of glutamatergic synapses, mainly localized in the cerebral cortex and the hippocampus, facilitates or reduces glutamatergic transmission by acting on neuronal AMPA and NMDA receptors, respectively. However, neurons are not the only targets of zinc. In the present study, we provide evidence that zinc inhibits protein synthesis in cultured astrocytes from the cerebral cortex of embryonic mice. This inhibition, which reached 85% in the presence of 100 micro m zinc, was partially and slowly reversible and resulted from the successive inhibition of the elongation and the initiation steps of the protein translation process. This was assessed by measuring the phosphorylation level of the elongation factor eEF-2 and of the alpha subunit of the initiation factor eIF-2. Due to the rapid turnover of connexin-43 that forms junction channels in cultured astrocytes, the zinc-induced decrease of protein synthesis led to a partial disappearance of connexin-43, which was associated with an inhibition of the cellular coupling in the astrocytic syncitium. In conclusion, zinc not only inhibits protein synthesis in neurons, as previously demonstrated, but also in astrocytes. The resulting decrease in the intercellular communication between astrocytes should alter the function of surrounding neurons as well as their survival.
Alirezaei
Mehrdad
M
INSERM U11, Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France.
Mordelet
Elodie
E
Rouach
Nathalie
N
Nairn
Angus C
AC
Glowinski
Jacques
J
Prémont
Joël
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018031:Connexin 43 / Q000096:biosynthesis* / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020652:Peptide Elongation Factor 2 / Q000096:biosynthesis / Q000187:drug effects; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D018031:Connexin 43; D004268:DNA-Binding Proteins; D007476:Ionophores; D020652:Peptide Elongation Factor 2; D014157:Transcription Factors; D015032:Zinc