Quantitative analysis of heme and hemoglobin for the detection of intravascular hemolysis.

Background: Intravascular hemolysis is associated with massive release of hemoglobin and consequently labile heme into the blood, resulting in prothrombotic and proinflammatory events in patients. Though heme is well-known to participate in these adverse effects, it is not monitored. Instead, haptoglobin and hemoglobin serve as clinical biomarkers.

In-depth structure-function profiling of the complex formation between clotting factor VIII and heme.

Background And Aims: Blood disorders, such as sickle cell disease, and other clinical conditions are often accompanied by intravascular hemolytic events along with the development of severe coagulopathies. Hemolysis, in turn, leads to the accumulation of Fe(II/III)-protoporphyrin IX (heme) in the intravascular compartment, which can trigger a variety of proinflammatory and prothrombotic reactions. As such, heme binding to the blood coagulation proteins factor VIII (FVIII), fibrinogen, and activated protein C with functional consequences has been demonstrated earlier.

Oxidation of hemoglobin in the lung parenchyma facilitates the differentiation of pneumococci into encapsulated bacteria.

Unlabelled: Pneumococcal pneumonia causes cytotoxicity in the lung parenchyma but the underlying mechanism involves multiple factors contributing to cell death. Here, we discovered that hydrogen peroxide produced by (Spn-H O ) plays a pivotal role by oxidizing hemoglobin, leading to its polymerization and subsequent release of labile heme. At physiologically relevant levels, heme selected a population of encapsulated pneumococci.

Insights into the molecular basis and mechanism of heme-triggered TLR4 signalling: The role of heme-binding motifs in TLR4 and MD2.

Haemolytic disorders, such as sickle cell disease, are accompanied by the release of high amounts of labile heme into the intravascular compartment resulting in the induction of proinflammatory and prothrombotic complications in affected patients. In addition to the relevance of heme-regulated proteins from the complement and blood coagulation systems, activation of the TLR4 signalling pathway by heme was ascribed a crucial role in the progression of these pathological processes. Heme binding to the TLR4-MD2 complex has been proposed recently, however, essential mechanistic information of the processes at the molecular level, such as heme-binding kinetics, the heme-binding capacity and the respective heme-binding sites (HBMs) is still missing.

Shapes and Patterns of Heme-Binding Motifs in Mammalian Heme-Binding Proteins.

Heme is a double-edged sword. On the one hand, it has a pivotal role as a prosthetic group of hemoproteins in many biological processes ranging from oxygen transport and storage to miRNA processing. On the other hand, heme can transiently associate with proteins, thereby regulating biochemical pathways.

Exploring the Complex Network of Heme-Triggered Effects on the Blood Coagulation System.

Excess labile heme, occurring under hemolytic conditions, displays a versatile modulator in the blood coagulation system. As such, heme provokes prothrombotic states, either by binding to plasma proteins or through interaction with participating cell types. However, despite several independent reports on these effects, apparently contradictory observations and significant knowledge gaps characterize this relationship, which hampers a complete understanding of heme-driven coagulopathies and the development of suitable and specific treatment options.

Host and viral proteins involved in SARS-CoV-2 infection differentially bind heme.

In most severe cases, SARS-CoV-2-induced autoimmune reactions have been associated with hemolytic complications. Hemolysis-derived heme from ruptured red blood cells has been shown to trigger a variety of fatal proinflammatory and procoagulant effects, which might deteriorate the progression of COVID-19. In addition, the virus itself can induce proinflammatory signals via the accessory protein 7a.

Heme Determination and Quantification Methods and Their Suitability for Practical Applications and Everyday Use.

Many research institutions, clinical diagnostic laboratories, and blood banks are desperately searching for a possibility to identify and quantify heme in different physiological and pathological settings as well as various research applications. The reasons for this are the toxicity of the heme and the fact that it acts as a hemolytic and pro-inflammatory molecule. Heme only exerts these severe and undesired effects when it is not incorporated in hemoproteins.