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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-10-30
pubmed:abstractText
The immune response can be triggered by molecules derived from microorganisms (PAMP) or from molecules derived from damaged or dead host cells, known as the damage-associated molecular-pattern molecules (DAMP). Their immune effects are accompanied by altered redox environment. The level of stable end products of nitric oxide (NO)- plasma nitrate and nitrite (NOx), carbonyl groups (PCO) and nitrotyrosine (NTY), in relation to the metabolism of dsRNAs (poly I:C and poly A:U) and xanthine oxidase (XO activity), in plasma of type2 diabetic patients was determined. Thirty-six patients with type 2 diabetes (age group 34-66 years, 19 male and 17 female) were allocated to the study. Diabetic patients had a significantly higher level of plasma NOx products, NTY and PCO, fructosamine (FA) and XO activity indicating about altered redox environment. The concentration of circulating ribonucleic acids (CNAs) was significantly higher in type 2 diabetic patients, which was accompanied by a significantly decreased activity of RNase against double stranded RNA forms (poly I:C and poly A:U), compared to control samples. To determine whether CNAs, as possible DAMP molecules, are capable of exerting effect on inflammatory and host antiviral response, the effect of isolated CNAs on NF-kappaB, Bcl-2, Bax, MDA-5 and IRF-3 regulation was evaluated in culture of fresh isolated thymocytes. Circulating nucleic acids isolated from type 2 diabetic patients were able to upregulate NF-kappaB more than control RNA samples. In the same experimental conditions the mild Bcl-2 upregulation, followed by the marked Bax upregulation, was demonstrated. Since the Bcl-2/Bax ratio was lower in type 2 diabetic samples, obtained results may implicate that CNAs may exert proapoptotic response in type 2 diabetes. The CNAs isolated from diabetic patients were able to downregulate MDA-5 and IRF-3, very important subjects of the surveillance and cellular anti-viral response. The major findings of the present study are that impaired dsRNA metabolism may lead to increased level of different sized RNAs in type 2 diabetic patients. Acting as possible DAMP molecules, they may contribute to higher susceptibility of immune cells to inflammatory cascade via NF-kappaB activation, and possible MDA-5/IRF-3 axis downregulation, what may have an influence on further ineffective response against different pathogens.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3-nitrotyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose, http://linkedlifedata.com/resource/pubmed/chemical/DEAD-box RNA Helicases, http://linkedlifedata.com/resource/pubmed/chemical/IFIH1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-3, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Nitrites, http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Double-Stranded, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Xanthine Oxidase, http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1439-3646
pubmed:author
pubmed:copyrightInfo
J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart New York.
pubmed:issnType
Electronic
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
480-5
pubmed:meshHeading
pubmed-meshheading:19358092-Adult, pubmed-meshheading:19358092-Aged, pubmed-meshheading:19358092-Animals, pubmed-meshheading:19358092-Blood Glucose, pubmed-meshheading:19358092-Cells, Cultured, pubmed-meshheading:19358092-DEAD-box RNA Helicases, pubmed-meshheading:19358092-Diabetes Mellitus, Type 2, pubmed-meshheading:19358092-Female, pubmed-meshheading:19358092-Fluorescent Antibody Technique, pubmed-meshheading:19358092-Humans, pubmed-meshheading:19358092-Inflammation, pubmed-meshheading:19358092-Interferon Regulatory Factor-3, pubmed-meshheading:19358092-Male, pubmed-meshheading:19358092-Middle Aged, pubmed-meshheading:19358092-NF-kappa B, pubmed-meshheading:19358092-Nitrites, pubmed-meshheading:19358092-Nucleic Acids, pubmed-meshheading:19358092-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:19358092-RNA, Double-Stranded, pubmed-meshheading:19358092-RNA Stability, pubmed-meshheading:19358092-Rats, pubmed-meshheading:19358092-Thymus Gland, pubmed-meshheading:19358092-Tyrosine, pubmed-meshheading:19358092-Xanthine Oxidase, pubmed-meshheading:19358092-bcl-2-Associated X Protein
pubmed:year
2009
pubmed:articleTitle
Possible impact of impaired double-stranded RNA degradation and nitrosative stress on immuno-inflammatory cascade in type 2 diabetes.
pubmed:affiliation
Department of Biochemistry, Bul Dr Zorana Djindjica 81, 18 000 Nis, Serbia. kocicrg@yahoo.co.uk
pubmed:publicationType
Journal Article