In Vivo Level of Poly(ADP-ribose)

PolyADP-ribosylation is a post-translational modification that plays key roles in cellular physiological functions and DNA damage responses. PolyADP-ribosylation is finely and dynamically regulated by various enzymes and factors involved in the synthesis and degradation of poly(ADP-ribose) (PAR). To...

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Bibliographic Details
Published inChallenges (Basel) Vol. 9; no. 1; p. 23
Main Authors Miwa, Masanao, Ida, Chieri, Yamashita, Sachiko, Kouyama, Kenichi, Kuroda, Yasuhito, Eguchi, Takayuki, Ohta, Narumi, Sato, Teruaki, Tsuda, Masataka, Tanaka, Masakazu
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 22.05.2018
Subjects
Adenosine diphosphate
Artefacts
BRCA1 protein
Breast cancer
Cancer
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
ELISA
Enzymes
In vivo methods and tests
Inhibitors
LC-MS/MS
Lethality
Life sciences
Low level
Organs
Ovarian cancer
PARG
PARP
PARP inhibitor
Physiology
Poly(ADP-ribose)
polyADP-ribosylation
Polymers
Post-translation
Proteins
radioimmunoassay
Researchers
Ribose
Ribosylation
Sample preparation
Sensitivity
Signal transduction
Japan
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Summary:PolyADP-ribosylation is a post-translational modification that plays key roles in cellular physiological functions and DNA damage responses. PolyADP-ribosylation is finely and dynamically regulated by various enzymes and factors involved in the synthesis and degradation of poly(ADP-ribose) (PAR). To better understand the function of polyADP-ribosylation, it is necessary to quantify and monitor the change of the in vivo level of PAR, the product of polyADP-ribosylation, which is rapidly turning over and kept in quite low level in cells or in organs. Recent developments of potent inhibitors of polyADP-ribosylation is expected to kill BRCA1/2-mutated breast cancer cells and ovarian cancer cells (synthetic lethality). To know the efficacy of these inhibitors in vivo, it is necessary to develop highly sensitive and reproducible methods to know PAR levels within cells or organs. However there have been several difficulties in measuring the physiologically low level of PAR without artefacts. Our experiments recently clarified that the method of sample preparation is very important in addition to the sensitivity and specificity. From reviewing the literature, including ours, we would like to emphasize the importance of the procedures of sample preparation for the assay, in addition to the sensitivity by comparing the reported PAR levels in vivo.
ISSN:2078-1547
2078-1547
DOI:10.3390/challe9010023