Proinflammatory and proapoptotic effects of methylglyoxal on neutrophils from patients with type 2 diabetes mellitus

Wang, Hui; Meng, Qing H.; Gordon, John; Khandwala, Hasnain; Wu, Lingyun

doi:10.1016/j.clinbiochem.2007.07.016

Cited by 120 publications

(108 citation statements)

References 24 publications

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“…The translocation of pro-apoptotic proteins such as caspases to mitochondrial outer membrane has been demonstrated to precede nuclear DNA fragmentation and apoptosis in neutrophils [29]. Furthermore, type 2 diabetic neutrophils possess highly deregulated mitochondrial morphology with putative involvement in apoptosis [30]. In the present study, activation of caspase-3 measured cytometrically recorded significant higher apoptotic index in both early and late diabetic groups compared with healthy controls (Fig.…”

Section: Discussionsupporting

confidence: 61%

Impairment of Mitochondrial–Nuclear Cross Talk in Neutrophils of Patients with Type 2 Diabetes Mellitus

Khan

Raghuram²,

Pathak

et al. 2013

Ind J Clin Biochem

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Increased leukocyte apoptosis is intrinsically linked to disease patho-physiology, susceptibility to and severity of infections in type 2 diabetes mellitus (T2DM) patients. A consistent defect in neutrophil function is considered central to this increased risk for infections. Although redox imbalance is considered a potential mediator of these associated complications, detailed molecular evidence in clinical samples remains largely undetected. The study consisted of three groups (n = 50 each) of Asian Indians: early diagnosed diabetic patients, cases with late-onset diabetic complications and age and gender-matched healthy controls. We evaluated mitochondrial oxidative stress, levels of nuclear DNA damage and apoptosis in peripheral blood neutrophils isolated from T2DM patients. We observed that in both early and late diabetic subjects, the HbA1c levels in neutrophils were altered considerably with respect to healthy controls. Increased oxidative stress observed in both early and late diabetics imply the disentanglement of fine equilibrium of mitochondria-nuclear cross talk which eventually effected the augmentation of downstream nuclear cH2AX activation and caspase-3 expression. It would be overly naïve to refute the fact that mitochondrial deregulation in neutrophils perturbs immunological balance in type 2 diabetic conditions. By virtue of our data, we posit that maneuvering mitochondrial function might offer a prospective and viable method to modulate neutrophil function in T2DM. Nevertheless, similar investigations from other ethnic groups in conjunction with experimental evidences would be a preeminent need. Obviously, our study might aid to comprehend this complex interplay between mitochondrial dysfunction and neutrophil homeostasis in T2DM.

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Section: Discussionsupporting

confidence: 61%

Impairment of Mitochondrial–Nuclear Cross Talk in Neutrophils of Patients with Type 2 Diabetes Mellitus

Khan

Raghuram²,

Pathak

et al. 2013

Ind J Clin Biochem

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“…We have shown that MG levels are elevated in the plasma, aorta and kidney of fructose-fed Sprague-Dawley rats and spontaneously hypertensive rats (SHR) [61,[63][64][65]. Patients with type 1 and type 2 diabetes have 2-6 fold higher plasma levels of MG compared to healthy people [67,68]. MG possibly plays a role in the pathogenesis of insulin resistance and type 2 diabetes as shown by several in vitro [69][70][71], and by our recent in vivo study in acute [66] and chronic MG-treated www.intechopen.com…”

Section: Free Radicals Rosmentioning

confidence: 99%

“…The reader is referred to our earlier review on MG and oxidative stress [17]. MG increases the formation of superoxide [94,[96][97][98][99], hydrogen peroxide and peroxynitrite [94,95,98,100], proinflammatory cytokines, such as interleukin 1 (IL-1 ) [101], interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-(TNF-) [67,101], in different cell types such as VSMCs [62,94,95], endothelial cells [102], rat kidney mesangial cells [97], rat hepatocytes [100], neutrophils [67,98], platelets [99], cultured neural cells from rat hippocampus [101], cultured cortical neurons [103], and SH-SY5Y neuroblastoma cells [104].…”

Section: Methylglyoxal and Oxidative Stressmentioning

confidence: 99%

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Aging: Drugs to Eliminate Methylglyoxal, a Reactive Glucose Metabolite, and Advanced Glycation Endproducts

Dhar¹,

Desai²

2012

Pharmacology

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“…The mechanisms underlying this have been investigated using both cell culture models and human ex-vivo studies, and involve impairment of the normal inflammatory response combined with hyperglycaemia-mediated alteration in lipid and protein function, leading to advanced glycation end products (AGEs) and methglyxol formation. Experiments in patients with both type 1 and type 2 diabetes have shown that increased inflammatory cytokine release may also play a role in this [71][72][73].…”

Section: Impaired Immune Functionmentioning

confidence: 99%

Diabetes mellitus and apoptosis: inflammatory cells

et al. 2009

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Since the early observation that similarities between thyroiditis and insulitis existed, the important role played by inflammation in the development of diabetes has been appreciated. More recently, experiments have shown that inflammation also plays a prominent role in the development of target organ damage arising as complications, with both elements of the innate and the adaptive immune system being involved, and that cytokines contributing to local tissue damage may arise from both infiltrating and resident cells. This review will discuss the experimental evidence that shows that inflammatory cellmediated apoptosis contributes to target organ damage, from beta cell destruction to both micro-and macro-vascular disease complications, and also how alterations in leukocyte turnover affects immune function.

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Proinflammatory and proapoptotic effects of methylglyoxal on neutrophils from patients with type 2 diabetes mellitus

Cited by 120 publications

References 24 publications

Impairment of Mitochondrial–Nuclear Cross Talk in Neutrophils of Patients with Type 2 Diabetes Mellitus

Impairment of Mitochondrial–Nuclear Cross Talk in Neutrophils of Patients with Type 2 Diabetes Mellitus

Aging: Drugs to Eliminate Methylglyoxal, a Reactive Glucose Metabolite, and Advanced Glycation Endproducts

Diabetes mellitus and apoptosis: inflammatory cells

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