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Tankyrase Activity in Organs and Tissues of Mice
A N Kuimov1, A S Zhozhikashvili, V N Manskikh
1Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia. kuimov@genebee.msu.su.
Abstract:
Tankyrase, one of the NAD+ ADP-ribosyltransferases, is a target for drugs developed for their anticancer and other pharmacological activities. We designed an assay for estimation of the inhibition or activation of the enzyme in preclinical studies. In mice, the highest specific activity of tankyrase was observed in thymus, spleen, pancreas, and bone marrow. In murine liver, tankyrase is active in ontogenesis and during reparative regeneration; however, the basal activity is hardly detectable in normal liver and most of other organs of adult animals. We suggest that tankyrase is a part of the tissue growth and repair machinery, while its age-dependent inhibition, when an organism stops growing, turns on phenoptosis.
Insights
Tankyrase, an enzyme involved in cell growth, shows high activity in specific mouse organs and during tissue repair. Its age-dependent inhibition may trigger phenoptosis, the process of aging.
Area of Science:
- Biochemistry
- Enzymology
- Pharmacology
Background:
- Tankyrase, a NAD+ ADP-ribosyltransferase, is a drug target for anticancer and pharmacological applications.
- Understanding tankyrase activity is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To design and implement an assay for evaluating tankyrase inhibition or activation in preclinical settings.
- To investigate the tissue-specific activity and developmental roles of tankyrase.
Main Methods:
- Development of a novel assay for tankyrase activity measurement.
- Analysis of tankyrase specific activity across various murine tissues and developmental stages.
Main Results:
- Highest tankyrase specific activity was detected in thymus, spleen, pancreas, and bone marrow in mice.
- Tankyrase exhibited activity during murine liver development and repair, with low basal levels in normal adult organs.
- Age-dependent inhibition of tankyrase was observed as organisms cease growth.
Conclusions:
- Tankyrase is implicated as a key component of the tissue growth and repair machinery.
- The age-dependent inhibition of tankyrase may initiate phenoptosis, contributing to the aging process.
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