title: Estrogen regulates energy metabolic pathway and upstream adenosine 5'-monophosphate-activated protein kinase and phosphatase enzyme expression in dorsal vagal complex metabolosensory neurons during glucostasis and hypoglycemia.
abstract: The ability of estrogen to shield the brain from the bioenergetic insult hypoglycemia is unclear. Estradiol (E) prevents hypoglycemic activation of the energy deficit sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) in hindbrain metabolosensory A2 noradrenergic neurons. This study investigates the hypothesis that estrogen regulates A2 AMPK through control of fuel metabolism and/or upstream protein kinase/phosphatase enzyme expression. A2 cells were harvested by laser microdissection after insulin or vehicle (V) injection of E- or oil (O)-implanted ovariectomized female rats. Cell lysates were evaluated by immunoblot for glycolytic, tricarboxylic acid cycle, respiratory chain, and acetyl-CoA-malonyl-CoA pathway enzymes. A2 phosphofructokinase (PFKL), isocitrate dehydrogenase, pyruvate dehydrogenase, and ATP synthase subunit profiles were elevated in E/V vs. O/V; hypoglycemia augmented PFKL and α-ketoglutarate dehydrogenase expression in E only. Hypoglycemia increased A2 Ca(2+) /calmodulin-dependent protein kinase-β in O and reduced protein phosphatase in both groups. A2 phospho-AMPK levels were equivalent in O/V vs. E/V but elevated during hypoglycemia in O only. These results implicate E in compensatory upregulation of substrate catabolism and corresponding maintenance of energy stability of A2 metabolosensory neurons during hypoglycemia, outcomes that support the potential viability of molecular substrates for hormone action as targets for therapies alleviating hypoglycemic brain injury.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, Louisiana.
authors.forename: Pratistha
authors.initials: P
authors.lastname: Tamrakar
authors.forename: Baher A
authors.initials: BA
authors.lastname: Ibrahim
authors.forename: Amit D
authors.initials: AD
authors.lastname: Gujar
authors.forename: Karen P
authors.initials: KP
authors.lastname: Briski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001016:Aortic Bodies / Q000473:pathology*; D001786:Blood Glucose; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D007003:Hypoglycemia / Q000188:drug therapy / Q000473:pathology*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D061346:Laser Capture Microdissection; D010052:Ovariectomy; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D004958:Estradiol; D014446:Tyrosine 3-Monooxygenase; D007655:Ketoglutarate Dehydrogenase Complex; D055372:AMP-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases
keywords: A2 noradrenergic neurons; PP2A; acetyl-CoA carboxylase; calcium/calmodulin kinase; fatty acid synthase; isocitrate dehydrogenase; laser-catapult microdissection; ovariectomy; phospho-AMPK; phosphofructokinase