Acrylamide stimulates glutamine uptake in Fischer 344 rat astrocytes by a mechanism involving upregulation of the amino acid transport system N.
High demand of neoplastic tissues for glutamine (Gln) is met by its active transport across cell membranes. Chronic treatment with acrylamide in rodents is associated with an increased incidence of neoplasms, including astrocytomas. In this study, 24-h acrylamide treatment significantly increased the initial rate of l-[G-3H]glutamine uptake in astrocyte cultures derived from the acrylamide-sensitive Fischer 344 rat, and this effect could be fully inhibited by histidine, a model substrate for the amino acid transport system N. RT-PCR analysis revealed that acrylamide treatment caused a significant increase in the astrocytic expression of the mRNA coding for the major system N protein, SNAT3, which is specifically overexpressed in malignant gliomas in situ. The acrylamide-induced upregulation of astrocytic Gln transport via system N is likely to affect Gln homeostasis in these cells and may be causally related to the increased astrocytoma incidence observed in Fischer 344 rats.
Wu
Qi
Q
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Sidoryk
Marta
M
Mutkus
Lysette
L
Zielińska
Magdalena
M
Albrecht
Jan
J
Aschner
Michael
M
D020106:Acrylamide / Q000494:pharmacology*; D026905:Amino Acid Transport Systems / Q000096:biosynthesis*; D026921:Amino Acid Transport Systems, Neutral / Q000096:biosynthesis*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005973:Glutamine / Q000378:metabolism*; D006639:Histidine / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D012333:RNA, Messenger; C403222:system N protein 1; D005973:Glutamine; D020106:Acrylamide; D006639:Histidine