High glucose concentrations stimulate human monocyte sodium/hydrogen exchanger activity and modulate atherosclerosis-related functions

Koliakos, George; Zolota, Zacharoula; Paletas, Konstantinos; Kaloyianni, Martha

doi:10.1007/s00424-004-1340-z

Cited by 15 publications

(31 citation statements)

References 39 publications

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“…In our study, it has been detected that glucose can influence the de novo synthesis of non-glycated CD36 proteins, which appeared sooner and in higher levels when the glucose concentration was higher; this effect, however, seemed to be limited by time. Higher glucose concentration also inhibited glycated CD36 expression in healthy subjects, as has been reported [27], though other authors have found contrary results [23, 25]. Inhibition was shown since the beginning of the study and was not as important in monocytes cultured in lower glucose levels (EG conditions), which later showed a decrease in glycated CD36 protein expression.…”

Section: Discussionsupporting

confidence: 68%

CD36 overexpression: a possible etiopathogenic mechanism of atherosclerosis in patients with prediabetes and diabetes

López-Carmona

Plaza-Serón

Vargas-Candela

et al. 2017

Diabetol Metab Syndr

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RationaleCD36 is a scavenger receptor located on monocytes which is involved in foam cell transformation.AimTo evaluate CD36 expression under different glycemic states in both healthy subjects and in atherosclerotic patients.Subjects and methodsIn order to evaluate the possible effects of hyperglycemia on CD36 expression in healthy subjects, an in vitro experiment was carried out using monocyte in three different conditions: extreme hyperglycemia (HG), euglycemia (EG) and in the absence of glucose. On the other hand, three groups of atherosclerotic patients were evaluated according to their glycemic conditions: normoglycemic (NG), prediabetic (preDM) and diabetic (DM) patients. CD36 expression (mRNA, non-glycated and glycated protein) was analyzed in monocytes.ResultsCD36 mRNA expression in the in vitro experiment peaked at 4 and 24 h under HG conditions. No differences in mRNA levels were found in the EG and control group. The level of non-glycated proteins was higher in HG and EG conditions compared with control group. Glycated protein expression was inhibited by glucose in a sustained manner. In atherosclerotic patients, a significant association was observed when comparing glycated CD36 protein expression in DM with NG patients (p = 0.03). No significant differences were found in mRNA and non-glycated CD36 expression in these patients. Moreover, BMI, insulin, weight and treatment were shown to be related to CD36 expression (mRNA, non-glycated and glycated protein levels, depending of the case) in atherosclerotic patients.ConclusionsHyperglycemia is an important modulator of CD36 mRNA and non-glycated protein expression in vitro, increasing de novo synthesis in healthy subjects. In atherosclerotic patients, there are progressive increases in CD36 receptors, which may be due to a post-translational stimulus.

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Section: Discussionsupporting

confidence: 68%

CD36 overexpression: a possible etiopathogenic mechanism of atherosclerosis in patients with prediabetes and diabetes

López-Carmona

Plaza-Serón

Vargas-Candela

et al. 2017

Diabetol Metab Syndr

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“…This ubiquitously expressed isoform has a major housekeeping role through the regulation of intracellular pH (pHi) and cell volume via the exchange of extracellular Na + with H + in a 1:1 ratio (Putney et al 2002). Additionally, through its cytoplasmic C-terminal domains, NHE1 is known to interact with the cytoskeleton as well as a variety of cytoplasmic proteins, through which it accepts signals initiated by molecules such as glucose, hormones, and others which affect its activation (Bourikas et al 2003;Koliakos et al 2004). Through these interactions, NHE1 is both itself regulated and also able to regulate cellular functions such as cell motility and cell survival (Malo and Fliegel 2006).…”

Section: Introductionmentioning

confidence: 99%

The ambiguous role of the Na+–H+ exchanger isoform 1 (NHE1) in leptin-induced oxidative stress in human monocytes

Konstantinidis

Paletas

Koliakos

et al. 2009

Cell Stress and Chaperones

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Leptin, a 16-kDa cytokine produced mainly by the adipose tissue, is known to increase energy expenditure while at the same time lowering food intake by acting directly on the hypothalamus. ObRb, the leptin receptor mostly involved in intracellular signaling, is expressed in a wide range of tissues, thus allowing leptin to affect a much broader diversity of biological processes. High concentrations of leptin are encountered in patients with hyperleptinemia, a condition which very often accompanies obesity and which is a direct result of leptin resistance. In the present study, moderate and high concentrations of leptin (16 and 160 ng/ml) were mostly utilized in order to investigate the role of this cytokine in oxidative stress levels in human monocytes. Leptin was found to increase oxidative species production as measured with 2',7'-dichlorodihydrofluorescein diacetate (general marker of oxidative species, but not O2-*) and dihydroethidium (marker of O2-*). Surprisingly, it also augmented superoxide dismutase activity. Inhibition of the Na+-H+ exchanger isoform 1 (NHE1) also inhibited leptin-induced superoxide anion production but at the same time amplified leptin-induced production of other oxidative species. Signaling proteins such as phosphoinositide 3 kinase and conventional isoforms of protein kinase C (alpha-, beta(i)-, beta(ii)-), as well as NADPH oxidase, also participated in leptin signaling. Finally, leptin was found to increase glutathionylation levels of NHE1-bound heat shock protein 70 kDa (Hsp70) but not Hsp70 binding to NHE1.

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“…Transmigration of monocytes through laminin-1-coated filters was performed as previously described [18]. In brief, filters of 6.5 mm diameter, 5-µm pore Transwell culture inserts (Costar, Cambridge, Mass., USA) were coated with 20-µg/ml laminin-1 and left to dry overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Signaling Components Involved in Leptin-Induced Amplification of the Atherosclerosis-Related Properties of Human Monocytes

Konstantinidis

Paletas²,

Koliakos

et al. 2008

J Vasc Res

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Background/Aims: Leptin, a 16-kDa cytokine that is released mainly by the adipose tissue, is known to affect a wide assortment of processes, ranging from energy homeostasis to angiogenesis and the immune response. In the present study, the effect of leptin on atherosclerosis-related properties of human monocytes was investigated. Methods: Monocytes were isolated from whole blood obtained from healthy donors who had normal body mass index values. Pharmacological inhibition of specific signaling proteins was implemented. Fluorescence spectrometry and immunofluorescence techniques, as well as ELISA methods, were utilized. Leptin dose response curves were determined for each type of experiment. Results: Leptin (160 ng/ml) was found to augment monocyte adhesion to laminin-1 and its migration through this glycoprotein, which is one of the main components of the extracellular matrix. Additionally, leptin increased CD36-receptor surface expression, as well as moderately oxidized low-density lipoprotein (oxLDL₃) uptake levels. Conclusion: Leptin amplifies the pro-atheromatic properties of human monocytes through a complex signaling net which involves the Na⁺/H⁺ exchanger isoform-1, the actin cytoskeleton, phosphoinositide 3-kinase, certain conventional isoforms of protein kinase C and NADPH oxidase.

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High glucose concentrations stimulate human monocyte sodium/hydrogen exchanger activity and modulate atherosclerosis-related functions

Cited by 15 publications

References 39 publications

CD36 overexpression: a possible etiopathogenic mechanism of atherosclerosis in patients with prediabetes and diabetes

CD36 overexpression: a possible etiopathogenic mechanism of atherosclerosis in patients with prediabetes and diabetes

The ambiguous role of the Na+–H+ exchanger isoform 1 (NHE1) in leptin-induced oxidative stress in human monocytes

Signaling Components Involved in Leptin-Induced Amplification of the Atherosclerosis-Related Properties of Human Monocytes

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