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Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
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Soluble klotho induces the heat shock factor 1 through EGR1 expression
Soo-A Kim1, Nguyen Khanh Toan2, Sang-Gun Ahn2
1Department of Biochemistry, School of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea.
Biofactors (Oxford, England)
|April 4, 2024
Summary
Soluble klotho protein enhances cellular stress response by boosting Heat Shock Factor 1 (HSF1) and heat shock proteins (HSPs). This study reveals klotho
Area of Science:
- Molecular Biology
- Cellular Biology
- Aging Research
Background:
- Klotho is a key antiaging protein with diverse biological functions.
- Cellular stress response pathways are crucial for maintaining cellular health and longevity.
- The specific role of soluble klotho in stress response remains incompletely understood.
Purpose of the Study:
- To investigate the role of soluble klotho in cellular stress response pathways.
- To elucidate the molecular mechanisms by which soluble klotho influences stress response.
- To determine if soluble klotho can modulate Heat Shock Factor 1 (HSF1) and heat shock protein (HSP) expression.
Main Methods:
- Utilized klotho-deficient (kl-/-) mouse embryonic fibroblasts (MEFs).
- Administered recombinant soluble klotho to kl-/- MEFs.
- Assessed HSF1 levels, HSP expression (HSP90, HSP70, HSP27), cell proliferation, and HSF1 promoter activity.
- Employed point mutagenesis to identify transcription factor binding sites in the HSF1 promoter.
Main Results:
- Klotho deficiency significantly decreased HSF1 levels and impaired HSP expression.
- Recombinant soluble klotho treatment restored HSF1 levels and induced HSP expression in kl-/- MEFs.
- Soluble klotho promoted cell proliferation and HSF1 promoter activity in a concentration-dependent manner.
- Identified EGR1 as a transcription factor regulated by soluble klotho in the HSF1 promoter.
Conclusions:
- Soluble klotho plays a crucial role in cellular stress response pathways.
- Klotho directly interacts with the HSF1-mediated stress response pathway.
- Findings provide molecular insights into klotho's antiaging functions and its regulation of stress response.
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