title: Estradiol Regulates Dorsal Vagal Complex Signal Transduction Pathway Transcriptional Reactivity to the AMPK Activator 5-Aminoimidazole-4-Carboxamide-Riboside (AICAR).
abstract: The ovarian hormone estradiol (E) regulates effects of hindbrain adenosine 5'-monophosphate-activated protein kinase (AMPK) on caudal dorsal vagal complex (cDVC) neuron genomic activation and systemic glucostasis. The present study examined the hypothesis that cDVC signal transduction pathways exhibit distinctive E-dependent reactivity to activation of this sensor. RT-PCR microarray analysis was performed on RNA extracted from the cDVC of E- or oil (O)-implanted ovariectomized (OVX) adult female rats injected into the caudal fourth ventricle with the AMP mimetic 5-aminoimidazole-4-carboxamide-riboside (AICAR) (A) or saline (S). Microarray results show that the majority of marker genes differentially expressed in the E/S versus O/S cDVC were upregulated, as only myc (TGFβ; WNT pathways), bcl2 (Hedgehog pathway), and serpine (hypoxia pathway) mRNA profiles were downregulated by E. Several JAK/STAT and NFκB signaling pathway marker gene profiles were upregulated in O/A but unchanged in E/A; additional NFκB genes were inhibited by A in E but not O. Hypoxia and p53 pathways contain genes that were inhibited or stimulated in O/A, but unaltered in E/A. Conversely, TGFβ, p53, and NOTCH pathways each contained marker genes that were correspondingly modified or maintained in E/A versus O/A. Moreover, several oxidative stress pathway genes were suppressed in O/A while elevated or unchanged in E/A. Hedgehog, PPAR, and WNT signaling pathways were characterized by numerous examples of A-induced reversal of E augmentation of marker gene expression coinciding with opposite or no drug effects in O. Data presented here demonstrate that E exerts distinctive effects on cDVC signal transduction pathway marker gene reactivity to activated AMPK. Further research is needed to determine if observed changes in signal pathway marker gene transcription correlate with adjustments in gene product protein expression, and to characterize the role of aforementioned signaling pathways in E-sensitive cellular and systemic responses to hindbrain AMPK activation.
authors: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 356 Bienville Building, 1800 Bienville Drive, Monroe, LA, 71201, USA.
authors: Fahaad S H
authors: FSH
authors: Alenazi
authors: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 356 Bienville Building, 1800 Bienville Drive, Monroe, LA, 71201, USA.
authors: Baher A
authors: BA
authors: Ibrahim
authors: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 356 Bienville Building, 1800 Bienville Drive, Monroe, LA, 71201, USA. briski@ulm.edu.
authors: Karen P
authors: KP
authors: Briski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D053612:Janus Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051880:Receptors, Notch; D012265:Ribonucleotides; D050791:STAT Transcription Factors; D015843:Serpins; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D000620:Aminoimidazole Carboxamide; D004958:Estradiol; D053612:Janus Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide