title: Diabetes-causing gene, kruppel-like factor 11, modulates the antinociceptive response of chronic ethanol intake.
abstract: BACKGROUND
  Alcohol (EtOH [ethanol]) is an antinociceptive agent, working in part, by reducing sensitivity to painful stimuli. The transcription factor Kruppel-like factor 11 (KLF11), a human diabetes-causing gene that also regulates the neurotransmitter metabolic enzymes monoamine oxidase (MAO), has recently been identified as an EtOH-inducible gene. However, its role in antinociception remains unknown. Consequently, we investigated the function of KLF11 in chronic EtOH-induced antinociception using a genetically engineered knockout mouse model.
  
  
  METHODS
  Wild-type (Klf11(+/+) ) and KLF11 knockout (Klf11(-/-) ) mice were fed a liquid diet containing EtOH for 28 days with increasing amounts of EtOH from 0% up to a final concentration of 6.4%, representing a final diet containing 36% of calories primarily from EtOH. Control mice from both genotypes were fed liquid diet without EtOH for 28 days. The EtOH-induced antinociceptive effect was determined using the tail-flick test before and after EtOH exposure (on day 29). In addition, the enzyme activity and mRNA levels of MAO A and MAO B were measured by real-time RT-PCR and enzyme assays, respectively.
  
  
  RESULTS
  EtOH produced an antinociceptive response to thermal pain in Klf11(+/+) mice, as expected. In contrast, deletion of KLF11 in the Klf11(-/-) mice abolished the EtOH-induced antinociceptive effect. The mRNA and protein levels of KLF11 were significantly increased in the brain prefrontal cortex of Klf11(+/+) mice exposed to EtOH compared with control Klf11(+/+) mice. Furthermore, MAO enzyme activities were affected differently in Klf11 wild-type versus Klf11 knockout mice exposed to chronic EtOH. Chronic EtOH intake significantly increased MAO B activity in Klf11(+/+) mice.
  
  
  CONCLUSIONS
  The data show KLF11 modulation of EtOH-induced antinociception. The KLF11-targeted MAO B enzyme may contribute more significantly to EtOH-induced antinociception. Thus, this study revealed a new role for the KLF11 gene in the mechanisms underlying the antinociceptive effects of chronic EtOH exposure.
authors.affiliation: Department of Psychiatry and Human Behavior , University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Ou
authors.forename: Chinelo
authors.initials: C
authors.lastname: Udemgba
authors.forename: Niping
authors.initials: N
authors.lastname: Wang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Dai
authors.forename: Gwen
authors.initials: G
authors.lastname: Lomberk
authors.forename: Seungmae
authors.initials: S
authors.lastname: Seo
authors.forename: Raul
authors.initials: R
authors.lastname: Urrutia
authors.forename: Junming
authors.initials: J
authors.lastname: Wang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Duncan
authors.forename: Sharonda
authors.initials: S
authors.lastname: Harris
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Fairbanks
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D000700:Analgesics; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D003920:Diabetes Mellitus / Q000235:genetics*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D059225:Nociception / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011930:Reaction Time / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D000700:Analgesics; D051017:Apoptosis Regulatory Proteins; D002492:Central Nervous System Depressants; D004268:DNA-Binding Proteins; C506460:KLF11 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D000431:Ethanol; D008995:Monoamine Oxidase
keywords: Antinociceptive Response; Chronic Ethanol Intake; Gene Knockout; Kruppel-Like Factor 11 (Transforming Growth Factor-Beta-Inducible Early Gene 2); Mice; Monoamine Oxidase