| Interferon-gamma-inducible kynurenines/pteridines inflammation cascade: implications for aging and aging-associated psychiatric and medical disorders. | |
| | |
MedLine Citation:
|
PMID: 20811799 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
This review of literature and our data suggests that up-regulated production of interferon-gamma (IFNG) in periphery and brain triggers a merger of tryptophan (TRY)-kynurenine (KYN) and guanine-tetrahydrobiopterin (BH4) metabolic pathways into inflammation cascade involved in aging and aging-associated medical and psychiatric disorders (AAMPD) (metabolic syndrome, depression, vascular cognitive impairment). IFNG-inducible KYN/pteridines inflammation cascade is characterized by up-regulation of nitric oxide synthase (NOS) activity (induced by KYN) and decreased formation of NOS cofactor, BH4, that results in uncoupling of NOS that shifting arginine from NO to superoxide anion production. Superoxide anion and free radicals among KYN derivatives trigger phospholipase A2-arachidonic acid cascade associated with AAMPD. IFNG-induced up-regulation of indoleamine 2,3-dioxygenase (IDO), rate-limiting enzyme of TRY-KYN pathway, decreases TRY conversion into serotonin (substrate of antidepressant effect) and increases production of KYN associated with diabetes [xanthurenic acid (XA)], anxiety (KYN), psychoses and cognitive impairment (kynurenic acid). IFNG-inducible KYN/pteridines inflammation cascade is impacted by IFNG (+874) T/A genotypes, encoding cytokine production. In addition to literature data on KYN/TRY ratio (IDO activity index), we observe neopterin levels (index of activity of rate-limiting enzyme of guanine-BH4 pathway) to be higher in carriers of high (T) than of low (A) producers alleles; and to correlate with AAMPD markers (e.g., insulin resistance, body mass index, mortality risk), and with IFN-alpha-induced depression in hepatitis C patients. IFNG-inducible cascade is influenced by environmental factors (e.g., vitamin B6 deficiency increases XA formation) and by pharmacological agents; and might offer new approaches for anti-aging and anti-AAMPD interventions. |
| | |
Authors:
|
Gregory F Oxenkrug |
Related Documents
:
|
17159149 - Delay of t cell senescence by caloric restriction in aged long-lived nonhuman primates. 19017989 - Aging mice exhibit a functional defect in mucosal dendritic cell response against an in... 17513739 - Distinct subsets of foxp3+ regulatory t cells participate in the control of immune resp... 11466359 - Sendai virus fusion protein mediates simultaneous induction of mhc class i/ii-dependent... 12220529 - Effects of cadmium and zinc on solar-simulated light-irradiated cells: potential role o... 11714799 - The impact of h2-dm on humoral immune responses. 2192699 - Tumour necrosis factor in surgical illness. 11454399 - How immunology is reshaping clinical disciplines: the example of haematology. 18785209 - Protective effect of juzen-taiho-to on hepatocarcinogenesis is mediated through the inh... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-02 |
Journal Detail:
|
Title: Journal of neural transmission (Vienna, Austria : 1996) Volume: 118 ISSN: 1435-1463 ISO Abbreviation: J Neural Transm Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2011-01-25 Completed Date: 2011-04-25 Revised Date: 2012-01-04 |
Medline Journal Info:
|
Nlm Unique ID: 9702341 Medline TA: J Neural Transm Country: Austria |
Other Details:
|
Languages: eng Pagination: 75-85 Citation Subset: IM |
Affiliation:
|
Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University/Tufts Medical Center, Boston, MA, USA. goxenkrug@tuftsmedicalcenter.org |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aging
/
genetics,
physiology* Animals Humans Inflammation / genetics, pathology* Interferon-gamma / pharmacology* Kynurenine / metabolism, physiology* Mental Disorders / genetics, pathology* Metabolic Syndrome X / genetics, metabolism Obesity / genetics, pathology Polymorphism, Genetic / genetics Pteridines / metabolism* Signal Transduction / drug effects |
| Grant Support | |
ID/Acronym/Agency:
|
MH083225/MH/NIMH NIH HHS; R21 MH083225-02/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Pteridines; 343-65-7/Kynurenine; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Anatomic study of the axillary nerve in a Chinese cadaveric population: correlation of the course of...
Next Document: PROlocalizer: integrated web service for protein subcellular localization prediction.