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Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Oxidative stress modulates KLF6Full and its splice variants
Raquel Urtasun1, Francisco Javier Cubero, Natalia Nieto
1Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA.
Alcoholism, Clinical and Experimental Research
|April 11, 2012
Summary
Reactive oxygen species (ROS) increase Krüppel-like factor 6 (KLF6) expression and its variants, impacting liver injury. KLF6 variant V1 regulates TNFα, a key inflammatory mediator.
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Background:
- Alcohol hepatotoxicity involves reactive oxygen species (ROS) induction.
- Krüppel-like factor 6 (KLF6) is an early injury-responsive gene, but ROS and alcohol effects on its expression are unknown.
Purpose of the Study:
- Investigate ROS sources (CYP2E1, NQO1) and alcohol's role in KLF6 expression and splicing.
- Determine the effect on TNFα as a downstream target.
Main Methods:
- Utilized HepG2 cells with varying ROS production and primary hepatocytes.
- Administered pro-oxidants (arachidonic acid, menadione), inhibitors (diallylsulfide, NQO1 inhibitor), and antioxidants.
- Analyzed KLF6(Full), KLF6_V1, KLF6_V2 mRNA/protein expression and TNFα levels.
- Examined effects of alcohol feeding in rats and kinase phosphorylation inhibition (p38, JNK, ERK1/2).
Main Results:
- ROS, CYP2E1, and NQO1 modulated KLF6(Full) expression and splicing.
- Pro-oxidants enhanced KLF6 variants; effects blocked by Vitamin E and CYP2E1 inhibitor.
- Alcohol-fed rats showed increased KLF6(Full) mRNA.
- Kinase inhibition differentially affected KLF6 expression.
- KLF6_V1, not KLF6(Full), ablation increased TNFα, identifying it as a downstream target.
Conclusions:
- ROS significantly modulate KLF6 expression and splicing, contributing to liver injury.
- KLF6_V1 plays a role in TNFα regulation, highlighting its importance in inflammatory responses.
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