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Despite its important role in the central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>), the mechanisms controlling <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> expression in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> are largely unknown. Recent evidence, however, suggested that several stressors, such as hypoxia, acidosis, or oxidative stress, induce <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> expression. The present study was mainly aimed at determining whether and, if so, how glucose deprivation affects <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> expression in <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>12 cells. Initially, it was found that glucose deprivation gradually induced <jats:italic><jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content><\/jats:italic> gene expression in <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>12 cells. To elucidate the underlying molecular mechanisms, several intracellular signalings that were modified in response to glucose deprivation were examined. Both adenosine monophosphate kinase (<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>) activation and changes in osmotic pressure, which are modified by extracellular glucose concentration, had no effect on <jats:italic><jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content><\/jats:italic> gene expression; on the other hand, p38 activation in response to glucose deprivation played an important role in inducing <jats:italic><jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content><\/jats:italic> gene expression. It was also found that expression of sortilin, a <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> receptor implicated in <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> endocytosis, was dramatically reduced by glucose deprivation. In contrast to glucose\u2010dependent regulation of <jats:italic><jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content><\/jats:italic> gene expression, <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activation played a central role in reducing sortilin expression. Overall, the present study suggests that the <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content>\u2013sortilin axis is modulated by glucose deprivation via two distinct mechanisms. As <jats:styled-content style=\"fixed-case\">PGRN<\/jats:styled-content> is neuroprotective, this system may represent a new neuroprotective mechanism activated by glucose deprivation in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/2211-5463.12164","type":"journal-article","created":{"date-parts":[[2016,11,24]],"date-time":"2016-11-24T13:26:38Z","timestamp":1479993998000},"page":"149-159","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Glucose deprivation regulates the progranulin\u2013sortilin axis in <scp>PC<\/scp>12 cells"],"prefix":"10.1002","volume":"7","author":[{"given":"Ken\u2010ichi","family":"Kawashima","sequence":"first","affiliation":[{"name":"Graduate School of Life Sciences Toyo University Oura\u2010gun Gunma 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