Antithrombin and first complement protein recognize the same active heparin fraction

Calabrese, Graciela Cristina; Recondo, Eduardo; Recondo, Marta Elena Fernández de

doi:10.1016/s0049-3848(02)00062-2

Cited by 8 publications

(7 citation statements)

References 10 publications

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“…This inhibitory action of heparin on C1 esterase means T/N (%) = Total staining (staining grades 1-3)/number of rats in each group; PHR = partial hepatic resection; H = heparin. 1 Significant difference, 56% the lowest of all groups, p = 0.01. 2 Significant difference, 100% the highest of all groups, p = 0.01.…”

Section: Discussionmentioning

confidence: 94%

“…It operates as a cascade that amplifies inflammatory reactions as it progresses, as do the reactions that occur during blood coagulation [1] . Recent research has demonstrated that heparin exerts an anti-inflammatory effect on burns in humans and animals by inhibiting C1 esterase, an important enzyme in the complement cascade system [13,14] .…”

Section: Discussionmentioning

confidence: 99%

“…Eur Surg Res 2007;39: [216][217][218][219][220][221] 217 activation [1] . Blockage of the complement cascade by heparin is unrelated to the anticoagulant effects that heparin produces by inhibiting ATIII [2,3] .…”

Section: Role Of Heparin On Tnf-␣ and Il-6 Levels In Liver Regenerationmentioning

confidence: 99%

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Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Yuceturk

Yağmurdur²,

Gür

et al. 2007

Eur Surg Res

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Objectives: The aim of this study was to investigate the effect of heparin on TNF-α and interleukin (IL)-6 levels and the complement system in liver regeneration in a murine model. Materials and Methods: 32 Wistar albino female rats weighing between 180 and 250 g were included in the study. The rats were divided into four groups as follows: group 1, treated with partial (50%) hepatectomy and intravenous heparin 1,000 IU/kg in repeated daily doses; group 2, treated with sham operation and intravenous heparin 1,000 IU/kg in repeated daily doses; group 3, treated with partial (50%) hepatectomy, and group 4 (controls), treated with only sham operation. Before the surgical intervention and after a general anesthetic had been administered to all rats, blood was taken from the left ventricle of each rat, and each sample was assessed to determine total complement hemolytic activity (CH₅₀/ml). On the 5th postoperative day, blood was taken to assess CH₅₀ activity and the levels of TNF-α and IL-6 via ELISA. Each rat was then killed by decapitation after which gravimetric analysis and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) were performed. Results: Serum CH₅₀ activity of group 1 was 4% as compared to 51% in group 3 (p = 0.01). The serum TNF-α level of group 1 was 43 pg/ml as compared to 86 pg/ml in group 3 (p = 0.002). The serum IL-6 level of group 1 was 19 pg/ml as compared to 44 pg/ml in group 3 (p = 0.02). The serum IL-6 level of group 2 was 4 pg/ml as compared to 44 pg/ml in group 3 (p = 0.005). According to the results of gravimetric analysis, the mean regeneration rate of group 1 was 4.4% as compared to 22% of group 3 (p = 0.001). The mean PCNA index values of group 2 was the highest of all groups (p = 0.01). However, the mean PCNA index value of group 1 was the lowest of all groups (p = 0.01). Conclusion: Because of its anti-inflammatory action via the complement system, heparin produced an unfavorable effect on liver regeneration.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Yuceturk

Yağmurdur²,

Gür

et al. 2007

Eur Surg Res

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“…Heparin is also believed to directly bind to and inhibit C1 activity. There is evidence to suggest that C1 recognizes the fraction of heparin with high antithrombin III affinity 111. Heparin also has a profound effect on the complement cascade through its interaction with a number of other complement proteins 108…”

Section: Regulation Of Proteases and Esterasesmentioning

confidence: 99%

Heparin-Protein Interactions

Capila

Linhardt

2002

Angewandte Chemie International Edition

1,766

1,014

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Heparin, a sulfated polysaccharide belonging to the family of glycosaminoglycans, has numerous important biological activities, associated with its interaction with diverse proteins. Heparin is widely used as an anticoagulant drug based on its ability to accelerate the rate at which antithrombin inhibits serine proteases in the blood coagulation cascade. Heparin and the structurally related heparan sulfate are complex linear polymers comprised of a mixture of chains of different length, having variable sequences. Heparan sulfate is ubiquitously distributed on the surfaces of animal cells and in the extracellular matrix. It also mediates various physiologic and pathophysiologic processes. Difficulties in evaluating the role of heparin and heparan sulfate in vivo may be partly ascribed to ignorance of the detailed structure and sequence of these polysaccharides. In addition, the understanding of carbohydrate–protein interactions has lagged behind that of the more thoroughly studied protein–protein and protein–nucleic acid interactions. The recent extensive studies on the structural, kinetic, and thermodynamic aspects of the protein binding of heparin and heparan sulfate have led to an improved understanding of heparin–protein interactions. A high degree of specificity could be identified in many of these interactions. An understanding of these interactions at the molecular level is of fundamental importance in the design of new highly specific therapeutic agents. This review focuses on aspects of heparin structure and conformation, which are important for its interactions with proteins. It also describes the interaction of heparin and heparan sulfate with selected families of heparin‐binding proteins.

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“…Heparin bindet vermutlich direkt an C1 und inhibiert seine Aktivität. Es gibt Hinweise, dass C1 die Heparinfraktion erkennt, die eine hohe Affinität zu Antithrombin III hat 111. Durch seine Wechselwirkung mit einer Reihe anderer Komplementproteine hat Heparin zudem einen äußerst starken Effekt auf die Komplementkaskade 108…”

Section: Die Regulierung Von Proteasen Und Esterasenunclassified

Heparin-Protein-Wechselwirkungen

2002

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Heparin, ein zu den Glycosaminoglycanen gehörendes sulfatiertes Polysaccharid, zeigt eine Reihe wichtiger biologischer Wirkungen, die aus der Wechselwirkung mit Proteinen resultieren. Da Heparin die Geschwindigkeit erhöht, mit der Antithrombin die Serinproteasen in der Blutgerinnungskaskade inhibiert, findet es breite Anwendung als Antikoagulans (Antiblutgerinnungsmittel). Heparin und das strukturverwandte Heparansulfat sind komplizierte lineare Polymere, die aus Ketten unterschiedlicher Länge und Sequenz bestehen. Heparansulfat, das an den Oberflächen tierischer Zellen und in der extrazellulären Matrix ubiquitär ist, vermittelt ebenfalls eine Reihe physiologischer und pathophysiologischer Prozesse. Die Schwierigkeiten bei der Beurteilung der Rolle von Heparin und Heparansulfat in vivo können zum Teil auf die Unkenntnis der genauen Struktur und Sequenz dieser Polysaccharide zurückgeführt werden. Abgesehen davon weiß man über Kohlenhydrat‐Protein‐Wechselwirkungen viel weniger als über die eingehend untersuchten Protein‐Protein‐ und Protein‐Nucleinsäure‐Wechselwirkungen. Die neuere umfangreiche Forschung über strukturelle, kinetische und thermodynamische Aspekte der Proteinbindung von Heparin und Heparansulfat führte zu neuen Erkenntnissen über die Heparin‐Protein‐Wechselwirkungen. Viele dieser Wechselwirkungen sind hochspezifisch, deshalb ist es für die Entwicklung neuer Therapeutika von grundlegender Bedeutung, sie auf molekularer Ebene zu verstehen. Dieser Aufsatz konzentriert sich auf die strukturellen und konformativen Eigenschaften von Heparin, die für die Wechselwirkungen mit Proteinen wichtig sind, außerdem wird die Wechselwirkung von Heparin und Heparansulfat mit ausgewählten Heparin‐bindenden Proteingruppen behandelt.

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Antithrombin and first complement protein recognize the same active heparin fraction

Cited by 8 publications

References 10 publications

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Heparin-Protein Interactions

Heparin-Protein-Wechselwirkungen

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