Protein kinase C-mediated impairment of glutamine outward transport and SN1 transporter distribution by ammonia in mouse cortical astrocytes

Neurochemistry International
Katarzyna DąbrowskaMagdalena Zielińska

Abstract

SN1, a system N amino acid transporter specific for astrocytes, is mainly responsible for export of newly synthesized L-glutamine from the cells. Astrocytic retention of L-glutamine which plays a critical role in ammonia-induced astrocytic swelling resulting in brain edema, could be tentatively attributed to the impaired L-glutamine export from astrocytes. The present study demonstrates that treatment of cultured mouse cortical astrocytes for 24 h with 5 mM ammonium chloride ("ammonia") inhibits the system N-mediated L-glutamine transport out of the cell, and that this inhibition is related to the reduced presence of the SN1 transporter on the cell membrane. Ammonia decreased total protein kinase C (PKC) activity in the absence but not in the presence of PKC activator, phorbol 12-myristate 13-acetate (PMA), and activation of PKC by PMA reversed both the ammonia-induced decrease of system N-mediated L-glutamine release and ammonia-induced SN1 deficit in the membrane fraction. However, while ammonia did not change the protein level of PKCα isoform, it decreased the protein content of PKCδ. Moreover, ammonia treatment increased the cell surface expression of SN1 in cells with silenced PKCα and PKCδ. Silencing of PKCδ abrogated the...Continue Reading

Citations

Jan 13, 2019·International Journal of Molecular Sciences·Katarzyna Dąbrowska, Magdalena Zielińska

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.