Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPK-dependent pathway

Chang, Ping-Chuan; Chen, Tso Hsiao; Chang, Chun-Jen; Hou, Chun-Cheng; Chan, Paul; Lee, Horng Mo

doi:10.1111/j.1523-1755.2004.00602.x

Cited by 94 publications

(63 citation statements)

References 41 publications

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“…Currently, to our knowledge, there are no literature data related to RAGE involvement in ßA nitrergic system activation; however, it has been demonstrated that RAGE linkage with other ligands, as advanced glycation-end products (AGE), stimulated iNOS expression in mouse macrophages (37), in murine endothelial cells (38), and in murine macrophages (39). AGE stimulation led to nitrite accumulation and iNOS protein expression, which were partially downregulated by preincubation with anti-RAGE antibody, suggesting the role of RAGE in AGE-induced nitrosative stress activation (39,40).…”

Section: Discussionmentioning

confidence: 99%

Involvement of the receptor for advanced glycation-end products (RAGE) in β-amyloid-induced toxic effects in rat cerebromicrovascular endothelial cells cultured in vitro

Baiguera

Fioravanzo²,

Grandi³

et al. 2009

Int J Mol Med

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Abstract. To ascertain whether the potential biological effects of ß amyloid (ßA) on the endothelium are partly mediated by the receptor for advanced glycation-end products (RAGE), we performed a series of experiments which analyzed the effects of the ßA peptide on in vitro cerebromicrovascular endothelial cells (CECs). Our results suggest that RAGE is directly responsible for ßA actions on CECs, such as its toxic effect on cell survival, viability and angiogenic capability. We observed that a 6-h incubation period exposing CECs to ßA increased the extracellular levels of nitrite. Furthermore, the presence of a nitric oxide synthase inhibitor, L-NAME, was able to enhance CEC survival and viability. Immunocytochemical analyses demonstrated that the peptide induced expression of the inducible form of NOS, iNOS, typically synthesized in response to immune/inflammatory stimuli. Upon blocking the interaction of ßA and RAGE, we observed significantly decreased levels of NO and suppression of iNOS immunoreactivity. In conclusion, our data suggest the involvement of RAGE, at least partly, in mediating the effects of ßA on CECs. In particular, the decrease of in vitro cell viability and functionality and nitrosative stress activation was inhibited by blocking ßA (1-42) -RAGE interaction.

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Section: Discussionmentioning

confidence: 99%

Involvement of the receptor for advanced glycation-end products (RAGE) in β-amyloid-induced toxic effects in rat cerebromicrovascular endothelial cells cultured in vitro

Baiguera

Fioravanzo²,

Grandi³

et al. 2009

Int J Mol Med

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“…Intracellular responses unleash important physiological effects, such as being a potent vasodilator with effects on both blood pressure regulation and renal function 2,54 . Recent studies have shown that AGEs induce iNOS expression in mesangial cells by activation of cytokines 2 -NF-kB and p38 MAPK 54,56 . Mesangial cells cultured in high glucose medium showed an increase in iNOS expression related to expansion of extracellular fibronectin 52,53,55 .…”

Section: Diabetic Kidney Diseasementioning

confidence: 99%

“…Moreover, its accumulation is involved in early and in late-stage renal disease 52,54 . Nitric Oxide has a very short half-life and is formed from L-arginine, in an oxidation reaction catalyzed by three nitric oxide synthases isoforms (NOS) 55,56 . Two NOS are calcium dependent, one expressed in endothelial cells (eNOS) and the other in neuronal cells (nNOS).…”

Section: Diabetic Kidney Diseasementioning

confidence: 99%

“…The increased expression of iNOS is generally associated to the inflammatory process that accompanies diabetic nephropathy, having no participation in normal renal hemodynamics. Moreover, the eNOS found in glomerular endothelial cells contributes significantly with nitric oxide to normal kidney function and can be involved in the early stages of nephropathy [55][56][57] . The importance of NFκB as a common mediator in the functional and structural changes observed in the pathophysiology of diabetes kidney disease is increasingly well established 58 .…”

Section: Diabetic Kidney Diseasementioning

confidence: 99%

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Role of advanced glycation end products in the onset of diabetic kidney disease complications

et al. 2017

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Advanced glycation end products are known to play an important role in diabetes complications, such as diabetic nephropathy. Most known pathways of diabetic complications involve oxidative stress, that have pivotal role in cell dysfunction onset and progression of angiopathies. This review will explore how AGEs cause endothelial dysfunction in diabetes and what current biochemical mechanisms have been proposed as an explanation for the development of diabetic nephropathy.

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“…Overproduction and accumulation of AGEs having a key role in aging has been shown to result in several structural and functional disorders [2,3]. Production of AGEs depends on the blood glucose concentration and the exposure time and may result directly from the hyperglycemia [4].…”

Section: Introductionmentioning

confidence: 99%

Functional Effects of Alagebrium (ALT-711)–Isolated Rat Carotid Artery

2017

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Objective: In our study, the effects of glycosylated protein cross-link breaker, alagebrium was investigated on isolated rat carotid artery using myography. Alagebrium showed vasodilator effect on carotid artery rings; particularly, this effect was significantly increased in endothelium-intact rings. Materials and Methods:To clarify the vasodilator mechanism of alagebrium, different antagonists such as N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenclamide, indomethacin, metoprolol, propranolol, tetraethylammonium, and calcium channel activator BAYK-8644 were used to reverse this effect.Results: Relaxation% responses to alagebrium were more significantly increased in intact endothelium than in denuded arteries. Blocking vasodilation related to channels (K-ATP, PGI2, BKca) and receptors (ß1, ß2) did not reverse the relaxation response to alagebrium. Vasodilator response to alagebrium was only slightly decreased after L-NAME incubation and significantly decreased after BAYK-8644 incubation. Conclusion:Results of present study suggest that the mechanism of alagebrium-induced vasodilator effect may include the blockage of L-type calcium channels and partially of the nitric oxide synthase enzyme.Keywords: Alagebrium, calcium channel blockage, carotid artery, nitric oxide, vasodilatation ÖZ Amaç: Çalışmamızda, glikozile protein çapraz bağ kırıcısı olan alagebriumun sıçanlardan elde edilen karotis arter preparatları üzerindeki etkisi myograf yöntemi ile araştırılmıştır. Alagebrium karotis arter preparatlarında vazodilatör etki göstermiş ve bu etkinin özellikle endoteli sağlam damarlarda arttığı gözlenmiştir.Gereç ve Yöntem: Alagebriumun vazodilatör mekanizmasını aydınlatmak amacıyla N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenklamid, indometazin, metoprolol, propranolol, tetraetilamonyum gibi antagonistler ve kalsiyum kanal aktivatörü olan BAYK 8644 bu etkiyi geri çevirmek amacıyla kullanılmıştır. Bulgular: Alagebrium % gevşeme yanıtları, endoteli sağlam damarlarda endoteli bozulmuş damarlara göre anlamlı derecede artmıştır.. Vazodilatasyon ile ilgili kanalların (KATP, PGI2, BKca) ve reseptörlerin (ß1,ß2) bloke edilmesi de alagebrium un gevşeme yanıtını geri çevirememiştir. Alagebriuma vazodilatör cevap L-NAME uygulanması ile hafif derecede azalırken BAYK-8644 uygulanması ile anlamlı derecede azalmıştır.Sonuç: Çalışmamızın sonuçları; alagebriuma bağlı vazodilatör etki mekanizmasının L-tipi kalsiyum kanal blokajı ve kısmen de nitrik oksit sentaz enzim blokajına bağlı olduğunu göstermektedir.Anahtar Kelimeler: Alagebrium, nitrik oksit, kalsiyum kanal blokajı, karotis arter, vazodilatasyon Eurasian J Med 2017; 49: 188-92

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Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPK-dependent pathway

Abstract: These data suggest that cytokine release, NF-kappaB and p38 MAPK-dependent pathways may play a role in AGE-induced iNOS expression and subsequent nitric oxide production in mesangial cells. Rosiglitazone may prevent AGE-induced iNOS expression by interfering with p38 MAPK activity.

Cited by 94 publications

References 41 publications

Involvement of the receptor for advanced glycation-end products (RAGE) in β-amyloid-induced toxic effects in rat cerebromicrovascular endothelial cells cultured in vitro

Involvement of the receptor for advanced glycation-end products (RAGE) in β-amyloid-induced toxic effects in rat cerebromicrovascular endothelial cells cultured in vitro

Role of advanced glycation end products in the onset of diabetic kidney disease complications

Functional Effects of Alagebrium (ALT-711)–Isolated Rat Carotid Artery

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