RNA oxidation

A novel mechanism and biomarker in type 2 diabetes

L. K. Kjaer, V. Cejvanovic, T. Henriken, I. Brandslund, Cramer Christensen, H. E. Poulsen

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Resumé

RNA modification has attracted increasing interest as it is realized that epitranscriptomics is important in disease development. In type 2 diabetes we have suggested that high urinary excretion of 8-oxo-2'-Guanosine (8oxoGuo), as a measure of global RNA oxidation, is associated with poor survival independent of classical risk factors [Diabetes Care 2011;34:2594]. To confirm this suggestion, we obtained a urine sample from a cohort of 2778 type 2 diabetics and followed them for a median of 6.3 years. Cox regression survival analysis showed that the quartile with the highest 8oxoGuo excretion had a 2.9 significant hazard ratio for death compared with the quartile with the lowest 8oxoGuo excretion when adjusted for age, sex, BMI, smoker status, s-HbA1c, urine protein excretion and s-cholesterol. We conclude that it is now established that RNA oxidation is an independent risk factor for death in type 2 diabetes. In agreement with our previous finding, DNA oxidation did not show any prognostic value. RNA oxidation represents oxidative stress intracellularly, presumably predominantly in the cytosol. The mechanism of RNA oxidation is not clear, but hypothesized to result from mitochondrial dysfunction in diabetes resulting from the diabetic state, a dysfunction that includes increased production of hydrogen peroxide. We suggest that the intracellular RNA oxidation is compartmentalized from the traditional biomarkers in the extracellular compartment, and therefore provides independent prognostic value. It is possible that oxidized RNA is a novel disease mechanism, because of evidence that RNA modification can result in formation of truncated and/or modified proteins. RNA oxidation may therefore not only be a clinically usable biomarker in the clinical situation, but may also be a novel mechanism for development of late complications in type 2 diabetes.
OriginalsprogEngelsk
Artikelnummer32
TidsskriftFree Radical Biology & Medicine
Vol/bind87
Udgave nummerS1
Sider (fra-til)S25
Antal sider1
ISSN0891-5849
DOI
StatusUdgivet - 2015
Begivenhed22nd Annual Meeting of the Society for Free Radical Biology and Medicine - Boston, MA , USA
Varighed: 18. nov. 201521. nov. 2015

Konference

Konference22nd Annual Meeting of the Society for Free Radical Biology and Medicine
LandUSA
ByBoston, MA
Periode18/11/201521/11/2015

Emneord

  • *oxidation *non insulin dependent diabetes mellitus *society diabetes mellitus excretion survival risk factor death smoking hazard ratio proportional hazards model urinary excretion disease course cytosol urinalysis protein urine level oxidative stress *biological marker *free radical *RNA guanosine cholesterol hemoglobin A1c hydrogen peroxide protein DNA

Citer dette

Kjaer, L. K., Cejvanovic, V., Henriken, T., Brandslund, I., Christensen, C., & Poulsen, H. E. (2015). RNA oxidation: A novel mechanism and biomarker in type 2 diabetes. Free Radical Biology & Medicine, 87(S1), S25. [32]. https://doi.org/10.1016/j.freeradbiomed.2015.10.069
Kjaer, L. K. ; Cejvanovic, V. ; Henriken, T. ; Brandslund, I. ; Christensen, Cramer ; Poulsen, H. E. / RNA oxidation : A novel mechanism and biomarker in type 2 diabetes. I: Free Radical Biology & Medicine. 2015 ; Bind 87, Nr. S1. s. S25.
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abstract = "RNA modification has attracted increasing interest as it is realized that epitranscriptomics is important in disease development. In type 2 diabetes we have suggested that high urinary excretion of 8-oxo-2'-Guanosine (8oxoGuo), as a measure of global RNA oxidation, is associated with poor survival independent of classical risk factors [Diabetes Care 2011;34:2594]. To confirm this suggestion, we obtained a urine sample from a cohort of 2778 type 2 diabetics and followed them for a median of 6.3 years. Cox regression survival analysis showed that the quartile with the highest 8oxoGuo excretion had a 2.9 significant hazard ratio for death compared with the quartile with the lowest 8oxoGuo excretion when adjusted for age, sex, BMI, smoker status, s-HbA1c, urine protein excretion and s-cholesterol. We conclude that it is now established that RNA oxidation is an independent risk factor for death in type 2 diabetes. In agreement with our previous finding, DNA oxidation did not show any prognostic value. RNA oxidation represents oxidative stress intracellularly, presumably predominantly in the cytosol. The mechanism of RNA oxidation is not clear, but hypothesized to result from mitochondrial dysfunction in diabetes resulting from the diabetic state, a dysfunction that includes increased production of hydrogen peroxide. We suggest that the intracellular RNA oxidation is compartmentalized from the traditional biomarkers in the extracellular compartment, and therefore provides independent prognostic value. It is possible that oxidized RNA is a novel disease mechanism, because of evidence that RNA modification can result in formation of truncated and/or modified proteins. RNA oxidation may therefore not only be a clinically usable biomarker in the clinical situation, but may also be a novel mechanism for development of late complications in type 2 diabetes.",
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Kjaer, LK, Cejvanovic, V, Henriken, T, Brandslund, I, Christensen, C & Poulsen, HE 2015, 'RNA oxidation: A novel mechanism and biomarker in type 2 diabetes', Free Radical Biology & Medicine, bind 87, nr. S1, 32, s. S25. https://doi.org/10.1016/j.freeradbiomed.2015.10.069

RNA oxidation : A novel mechanism and biomarker in type 2 diabetes. / Kjaer, L. K.; Cejvanovic, V.; Henriken, T.; Brandslund, I.; Christensen, Cramer; Poulsen, H. E.

I: Free Radical Biology & Medicine, Bind 87, Nr. S1, 32, 2015, s. S25.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

TY - ABST

T1 - RNA oxidation

T2 - A novel mechanism and biomarker in type 2 diabetes

AU - Kjaer, L. K.

AU - Cejvanovic, V.

AU - Henriken, T.

AU - Brandslund, I.

AU - Christensen, Cramer

AU - Poulsen, H. E.

PY - 2015

Y1 - 2015

N2 - RNA modification has attracted increasing interest as it is realized that epitranscriptomics is important in disease development. In type 2 diabetes we have suggested that high urinary excretion of 8-oxo-2'-Guanosine (8oxoGuo), as a measure of global RNA oxidation, is associated with poor survival independent of classical risk factors [Diabetes Care 2011;34:2594]. To confirm this suggestion, we obtained a urine sample from a cohort of 2778 type 2 diabetics and followed them for a median of 6.3 years. Cox regression survival analysis showed that the quartile with the highest 8oxoGuo excretion had a 2.9 significant hazard ratio for death compared with the quartile with the lowest 8oxoGuo excretion when adjusted for age, sex, BMI, smoker status, s-HbA1c, urine protein excretion and s-cholesterol. We conclude that it is now established that RNA oxidation is an independent risk factor for death in type 2 diabetes. In agreement with our previous finding, DNA oxidation did not show any prognostic value. RNA oxidation represents oxidative stress intracellularly, presumably predominantly in the cytosol. The mechanism of RNA oxidation is not clear, but hypothesized to result from mitochondrial dysfunction in diabetes resulting from the diabetic state, a dysfunction that includes increased production of hydrogen peroxide. We suggest that the intracellular RNA oxidation is compartmentalized from the traditional biomarkers in the extracellular compartment, and therefore provides independent prognostic value. It is possible that oxidized RNA is a novel disease mechanism, because of evidence that RNA modification can result in formation of truncated and/or modified proteins. RNA oxidation may therefore not only be a clinically usable biomarker in the clinical situation, but may also be a novel mechanism for development of late complications in type 2 diabetes.

AB - RNA modification has attracted increasing interest as it is realized that epitranscriptomics is important in disease development. In type 2 diabetes we have suggested that high urinary excretion of 8-oxo-2'-Guanosine (8oxoGuo), as a measure of global RNA oxidation, is associated with poor survival independent of classical risk factors [Diabetes Care 2011;34:2594]. To confirm this suggestion, we obtained a urine sample from a cohort of 2778 type 2 diabetics and followed them for a median of 6.3 years. Cox regression survival analysis showed that the quartile with the highest 8oxoGuo excretion had a 2.9 significant hazard ratio for death compared with the quartile with the lowest 8oxoGuo excretion when adjusted for age, sex, BMI, smoker status, s-HbA1c, urine protein excretion and s-cholesterol. We conclude that it is now established that RNA oxidation is an independent risk factor for death in type 2 diabetes. In agreement with our previous finding, DNA oxidation did not show any prognostic value. RNA oxidation represents oxidative stress intracellularly, presumably predominantly in the cytosol. The mechanism of RNA oxidation is not clear, but hypothesized to result from mitochondrial dysfunction in diabetes resulting from the diabetic state, a dysfunction that includes increased production of hydrogen peroxide. We suggest that the intracellular RNA oxidation is compartmentalized from the traditional biomarkers in the extracellular compartment, and therefore provides independent prognostic value. It is possible that oxidized RNA is a novel disease mechanism, because of evidence that RNA modification can result in formation of truncated and/or modified proteins. RNA oxidation may therefore not only be a clinically usable biomarker in the clinical situation, but may also be a novel mechanism for development of late complications in type 2 diabetes.

KW - oxidation non insulin dependent diabetes mellitus society diabetes mellitus excretion survival risk factor death smoking hazard ratio proportional hazards model urinary excretion disease course cytosol urinalysis protein urine level oxidative stress biolo

U2 - 10.1016/j.freeradbiomed.2015.10.069

DO - 10.1016/j.freeradbiomed.2015.10.069

M3 - Conference abstract in journal

VL - 87

SP - S25

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

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