Faculty Collaboration Database

Diabetes-causing gene, kruppel-like factor 11, modulates the antinociceptive response of chronic ethanol intake. Alcohol Clin Exp Res 2014 Feb;38(2):401-8

Date

01/17/2014

Pubmed ID

24428663

Pubmed Central ID

PMC5567722

DOI

10.1111/acer.12258

Scopus ID

2-s2.0-84893649158 (requires institutional sign-in at Scopus site)   4 Citations

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.

Author List

Ou XM, Udemgba C, Wang N, Dai X, Lomberk G, Seo S, Urrutia R, Wang J, Duncan J, Harris S, Fairbanks CA, Zhang X

Author

Gwen Lomberk PhD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alcoholism
Analgesics
Animals
Apoptosis Regulatory Proteins
Blotting, Western
Central Nervous System Depressants
DNA-Binding Proteins
Diabetes Mellitus
Ethanol
Male
Mice
Mice, Knockout
Monoamine Oxidase
Nociception
Pain Measurement
Prefrontal Cortex
RNA, Messenger
Reaction Time
Real-Time Polymerase Chain Reaction
Repressor Proteins
Transcription Factors