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Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage
- Source :
- Journal of the American Society of Nephrology. 25:2316-2326
- Publication Year :
- 2014
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2014.
-
Abstract
- Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis.
- Subjects :
- Male
medicine.medical_specialty
Adenosine
DNA damage
Population
Molecular Conformation
Apoptosis
Oxidative phosphorylation
Biology
medicine.disease_cause
Japan
RNA, Transfer
Up Front Matters
Internal medicine
medicine
Animals
Humans
Rats, Wistar
Renal Insufficiency, Chronic
Fragmentation (cell biology)
education
Aged
Mice, Knockout
education.field_of_study
Renal ischemia
RNA
General Medicine
Acute Kidney Injury
Middle Aged
Mice, Inbred C57BL
Oxidative Stress
Basic Research
Endocrinology
Toxic injury
Biochemistry
Nephrology
Case-Control Studies
Female
Oxidative stress
DNA Damage
Subjects
Details
- ISSN :
- 10466673
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology
- Accession number :
- edsair.doi.dedup.....b80961e78f0e80f975385702bf3c9cc8