| Role and clinical significance of lymphocyte mitochondrial dysfunction in type 2 diabetes mellitus. | |
| | |
MedLine Citation:
|
PMID: 22061042 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Lymphocyte homeostasis in type 2 diabetes mellitus (T2DM) is associated with increased susceptibility to infections. Mitochondrial oxidative stress is implicated primarily in the immune pathophysiology of diabetes; however, the molecular underpinnings of lymphocyte mitochondrial dysfunction and ensuing downstream cellular effects are hitherto unreported. Both in early diagnosed patients and patients with late complications, we observed an inverse correlation between mitochondrial DNA content in lymphocytes and hemoglobin A1 (HbA1c) levels. This relation established for the first time might serve as a general, yet direct, predictor or indicator for mitochondrial dysfunction in T2DM. Compared with controls, nuclear DNA damage response was higher (P ≤ 0.001) in diabetic subjects with increased accumulation of phospho-ataxia-telangiectasia (ATM), γ-H2AX, along with active recruitment of repair proteins (Mre11, Rad50, and Nbs1). A higher frequency (>2%) of stable chromosomal anomalies with loss of telomere integrity was observed in cases with late complications. A significant decrease (P ≤ 0.001) in enzyme activity of complex II, III, and IV of mitochondrial respiratory chain was evident in both diabetic groups in comparison with healthy controls. Activation in the cascade of nuclear factor kappa-beta (NF-κβ)-mediated feed-forward proinflammatory cytokine response was noted among T2DM subjects. Increased oxidative stress, mitochondrial membrane depolarization, activation of caspase-3, and PARP observed in diabetic groups indicated bax triggered mitochondrial mediated cellular apoptosis. Our results provide the first insights of lymphocyte mitochondrial dysfunction that might be helpful in explaining the clinical significance of immunologic perturbation observed in type 2 diabetic conditions. Our data also indicate that maneuvering through the mitochondrial function might be a viable, indirect method to modulate lymphocyte homeostasis in T2DM. |
| | |
Authors:
|
Saba Khan; Gorantla V Raghuram; Arpit Bhargava; Neelam Pathak; Dolly H Chandra; Subodh K Jain; Pradyumna K Mishra |
Publication Detail:
|
Type: Journal Article Date: 2011-09-13 |
Journal Detail:
|
Title: Translational research : the journal of laboratory and clinical medicine Volume: 158 ISSN: 1878-1810 ISO Abbreviation: Transl Res Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-11-08 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101280339 Medline TA: Transl Res Country: United States |
Other Details:
|
Languages: eng Pagination: 344-59 Citation Subset: AIM; IM |
Copyright Information:
|
Copyright © 2011 Mosby, Inc. All rights reserved. |
Affiliation:
|
Research Wing, Bhopal Memorial Hospital & Research Centre, Bhopal, India; Department of Biotechnology, Dr. HS Gour Central University, Sagar, India. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Efficient myogenic reprogramming of adult white fat stem cells and bone marrow stem cells by freshly...
Next Document: Patient-specific measures of a biomarker for the generation of individual reference intervals: hemog...