Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock

Reade, Michael C.; Clark, Megan F.; Young, John; Boyd, C. A. R.

doi:10.1042/cs1020645

Cited by 25 publications

(22 citation statements)

References 17 publications

(21 reference statements)

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“…In peripheral blood mononuclear cells (PBMCs) in nonpregnant subjects, transport systems y ϩ and y ϩ L have been identified, contributing 13.7% and 86.3%, respectively, to total cationic amino acid transport. 16 In sepsis, cationic amino acid (L-lysine) uptake has been dem-onstrated to be significantly increased in association with increased NO production. This has been demonstrated to be almost entirely because of increase in the activity of the y ϩ transporter (contribution to total uptake increased from 13.7% to 49.5%) with a corresponding induction of CAT-2 mRNA expression and no significant change in uptake by system y ϩ L. 16 In patients with chronic renal failure and uraemia (a condition associated with increased circulation of proinflammatory cytokines), alterations in the L-arginine-NO pathway in PBMCs are characterized by a significant increase in system y ϩ activity with no change in system y ϩ L activity.…”

mentioning

confidence: 99%

System y ⁺ Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia

et al. 2006

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Abstract-Systemic inflammation and oxidative stress are features of normal pregnancy and, in excess, contribute to the pathogenesis of preeclampsia. Inflammatory cell activation stimulates uptake of arginine (the precursor for nitric oxide) by transport system y ϩ , expression of one of its genes (CAT-2) together with inducible nitric oxide synthase, leading to nitric oxide production. We investigated whether these changes occur in peripheral blood mononuclear cells in normal pregnancy and are exaggerated in preeclampsia. Samples from matched trios of nonpregnant, normal pregnant, and preeclamptic women were studied. Arginine transport was characterized, and the expression of inducible nitric oxide synthase and cell-specific nitric oxide production were measured. Arginine uptake by system y ϩ was significantly increased (PϽ0.001) in peripheral blood mononuclear cells in normal pregnancy but not in preeclampsia. CAT-2 mRNA was not detected in cells from nonpregnant women but was detected in 3 of 10 normal pregnant and 8 of 10 of preeclamptic women (PϽ0.001). Inducible nitric oxide synthase protein expression was significantly increased in normal pregnant women (PϽ0.05) but not preeclamptic women. No significant differences in cell-specific nitric oxide production were observed. These changes confirm the predictions for normal pregnancy but not for preeclampsia in which, despite increases in CAT-2 expression, arginine uptake is not additionally increased. This may create a relative deficiency of arginine in PBMCs favoring superoxide and peroxynitrite production and contribute to oxidative and nitrosative stress in preeclampsia.

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mentioning

confidence: 99%

System y ⁺ Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia

et al. 2006

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“…KAT, ADMA'nın hem hücreden dışarıya salınmasında, hem de hücreye alınmasında görevlidir. Konjestif kalp yetmezliği, akut böbrek yetmezliği ve septik şok gibi bazı klinik durumlarda KAT ekspresyonunun değişmiş olduğu bildirilmiştir [22][23][24]. KAT tarafından dolaşıma taşınan ADMA'nın, biyolojik olarak aktif olup olmadığı veya yüksek plazma konsantrasyonunun yüksek hücre içi seviyelerin bir belirteci olup olmadığı bilinmemektedir.…”

Section: Adma'nın Yıkılmasıunclassified

Metabolism of asymmetric dimethylarginine and its clinical significance

Erbil¹,

Kurt²,

Yaman³

et al. 2012

Turk J Bioch

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ÖZETAsimetrik dimetilarjinin nitrik oksit sentaz enziminin endojen inhibitörüdür. Nitrik oksit endotel bağımlı vazodilatasyon, damar duvarındaki düz kas proliferasyonu, hücre-hücre etkileşimleri, platelet adezyon ve agregasyonunun inhibisyonu ile monosit adezyonu inhibisyonu gibi düzenleyici fonksiyonlara sahiptir. Arjinin amino asitinin modifiye bir formu olan asimetrik dimetilarjinin, metilenmiş proteinlerin proteolizi sonucu oluşur. Hücrede oluşan ve salınan net asimetrik dimetilarjinin miktarı, arjinin metilasyonu, metillenmiş arjinin içeren proteinlerin yıkımı, dimetilarjinin dimetilaminohidrolaz enzimi ile metabolizasyonu ve hücreden atılımı oranları arasındaki dengeye bağlıdır. Hücre içinde oluşan asimetrik dimetilarjininin neredeyse tamamı dimetilarjinin dimetilaminohidrolaz enzimi tarafından yıkılırken küçük miktardaki asimetrik dimetilarjinin, katyonik amino asit taşıyıcıları tarafından hücreden kan dolaşımına taşınır. Plazmaya geçen asimetrik dimetilarjinin ya böbreklerden değişime uğramadan idrar ile atılmakta ya da başlıca karaciğer ve böbrekte olmak üzere tekrar hücre içine alınarak dimetilarjinin dimetilaminohidrolaz enzimi tarafından metabolize edilmektedir. Plazma asimetrik dimetilarjinin seviyesi, çeşitli avantaj ve dezavantajları bulunması ile birlikte, yüksek performanslı sıvı kromatografisi, kütle spektrometresi ve ELISA ile ölçülebilir. Plazmadaki asimetrik dimetilarjininin biyolojik olarak aktif olup olmadığı kesin olarak bilinmemektedir. Ancak literatürde pek çok klinik durumda plazma asimetrik dimetilarjinin konsantrasyonunun yüksek olduğunu gösteren çalışmalar mevcuttur. Bölümümüzde yapılan klinik ve deneysel çalışmalarda da literatürle uyumlu olarak kronik böbrek hastalığı, hipertansiyon, endometriosis ve şizofreni hastalarında yüksek olarak bulunmuştur. Özellikle, nitrik oksit gibi, kardiyovasküler sistem üzerine birçok düzenleyici etkisi bulunan bir molekülün sentezini inhibe etmesi nedeni ile günümüzde yeni bir kardiyovasküler risk faktörü olarak değerlendirilmektedir. Endotel disfonksiyonuna yol açması ve endotel disfonksiyonun birçok hastalığın patogenezinde önemli olması, yakın gelecekte de asimetrik dimetilarjinin üzerine araştırmaların devam edeceğine işaret etmektedir. Anahtar Sözcükler: Asimetrik dimetilarjininin, nitrik oksit, dimetilarjinin dimetilaminohidrolaz, endotel disfonksiyonu Çıkar çatışması: Yazarların çıkar çatışması bulunmamaktadır. ABSTRACTAsymmetric dimethylarginine is an endogenous inhibitory of nitric oxide synthase enzyme. Nitric oxide has regulatory functions such as endothelial dependent vasodilatation, smooth muscle proliferation in vessel wall, cell-cell interactions, platelet aggregation and adhesion inhibition and monosit adhesion inhibition. Asymmetric dimethylarginine, a modified form of arginine amino acid, is produced by proteolysis of methylated proteins. Net amount of produced and released ADMA depends on the balance between arginine methylation, degradation of proteins containing methylated arginine and metabolism by the enzyme dimetilarjinin di...

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“…64 Altered expression of CAT has been implicated in several clinical conditions, including congestive heart failure, chronic and acute renal failure, and septic shock. [65][66][67] It has been shown that system yϩ is capable of transporting both ADMA and SDMA across the cell membrane. 68 Changes in the expression of CAT may therefore not only influence the interorgan transport and cellular uptake of arginine, but also of ADMA and SDMA.…”

Section: Role Of Amino Acid Transportersmentioning

confidence: 99%

ADMA metabolism and clearance

Teerlink

2005

Vasc Med

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International audienceThe plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is the resultant of many processes at cellular and organ levels. Post-translational methylation of arginine residues of proteins plays a crucial role in the regulation of their functions, which include processes such as transcription, translation and RNA splicing. Because protein methylation is irreversible, the methylation signal can be turned off only by proteolysis of the entire protein. Consequently, most methylated proteins have high turnover rates. Free ADMA, which is formed during proteolysis, is actively degraded by the intracellular enzyme dimethylarginine dimethylaminohydrolase (DDAH). Some ADMA escapes degradation and leaves the cell via cationic amino acid transporters. These transporters also mediate uptake of ADMA by neighboring cells or distant organs, thereby facilitating active interorgan transport. Clearance of ADMA from the plasma occurs in small part by urinary excretion, but the bulk of ADMA is degraded by intracellular DDAH, after uptake from the circulation. This review discusses the various processes involved in ADMA metabolism: protein methylation, proteolysis of methylated proteins, metabolism by DDAH, and interorgan transport. In addition, the role of the kidney and the liver in the clearance of ADMA is highlighted

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Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock

Cited by 25 publications

References 17 publications

System y ⁺ Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia

System y ⁺ Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia

Metabolism of asymmetric dimethylarginine and its clinical significance

ADMA metabolism and clearance

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Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock

Cited by 25 publications

References 17 publications

System y + Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia

System y + Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia

Metabolism of asymmetric dimethylarginine and its clinical significance

ADMA metabolism and clearance

Contact Info

Product

Resources

About

System y ⁺ Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia

System y ⁺ Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia