Generating S-Nitrosothiols from Hemoglobin

Roche, Camille J.; Cassera, María B.; Dantsker, David; Hirsch, Rhoda Elison; Friedman, Joel M.

doi:10.1074/jbc.m113.482679

Cited by 28 publications

(26 citation statements)

References 99 publications

(144 reference statements)

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“…71,72 A resolution of this issue has been attempted by modifying Hb molecule into becoming an NO carrier through S-nitrosylation of cysteine residues in the β-subunits of Hb or imparting the ability of enzymatic transformation of Hb into a source NO donor in presence of nitrites, but with limited success in vivo. 73 Natural RBCs contain enzymes like catalase (CAT) and superoxide dismutase (SOD) that help mitigate the oxidative stresses stemming from superoxide moieties in injured and ischemic tissues. Based on this rationale, in an interesting approach these enzymes have been crosslinked to polymerized Hb to form PolyHb-SOD-CAT, which showed combined advantages of long circulation time and reduced oxidative damage.…”

Section: B Rbc Substitutes and Oxygen Carrier Systemsmentioning

confidence: 99%

Bio‐inspired nanomedicine strategies for artificial blood components

Gupta

2017

WIREs Nanomed Nanobiotechnol

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Blood is a fluid connective tissue where living cells are suspended in non-cellular liquid matrix. The cellular components of blood render gas exchange (RBCs), immune surveillance (WBCs) and hemostatic responses (platelets), and the non-cellular components (salts, proteins etc.) provide nutrition to various tissues in the body. Dysfunction and deficiencies in these blood components can lead to significant tissue morbidity and mortality. Consequently, transfusion of whole blood or its components is a clinical mainstay in the management of trauma, surgery, myelosuppression and congenital blood disorders. However, donor-derived blood products suffer from issues of shortage in supply, need for type matching, high risks of pathogenic contamination, limited portability and shelf-life, and a variety of side-effects. While robust research is being directed to resolve these issues, a parallel clinical interest has developed towards bioengineering of synthetic blood substitutes that can provide blood’s functions while circumventing the above problems. Nanotechnology has provided exciting approaches to achieve this, using materials engineering strategies to create synthetic and semi-synthetic RBC substitutes for enabling oxygen transport, platelet substitutes for enabling hemostasis and WBC substitutes for enabling cell-specific immune response. Some of these approaches have further extended the application of blood cell-inspired synthetic and semi-synthetic constructs for targeted drug delivery and nanomedicine. The current article will provide a comprehensive review of the various nanotechnology approaches to design synthetic blood cells, along with a critical discussion of successes and challenges of the current state-of-art in this field.

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Section: B Rbc Substitutes and Oxygen Carrier Systemsmentioning

confidence: 99%

Bio‐inspired nanomedicine strategies for artificial blood components

Gupta

2017

WIREs Nanomed Nanobiotechnol

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“…These two hypotheses were built in large part on in vitro experimental results with little or no validated animal studies to support them. Exporting NO from the erythrocyte or from free Hb would not only be mechanistically difficult without intermediates [26] particularly in the view of the fact that Hb will rapidly and irreversibly consume NO [24]. In studies where large animals (swine) experiencing hemorrhagic shock that mimic battlefield conditions, nitrite infusion with HBOCs resulted in transient drop in blood pressure, but increased the risk of pulmonary complications including pulmonary edema and congestion [27].…”

Section: Mechanisms Of Hboc Toxicity: Current Hypothesesmentioning

confidence: 99%

Blood substitutes: why haven’t we been more successful?

Alayash

2014

Trends in Biotechnology

142

136

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Persistent safety concerns have stalled the development of viable hemoglobin (Hb)-based oxygen carriers (HBOCs). HBOCs have several advantages over human blood, including availability, long-term storage and lack of infectious risk. The basis of HBOC toxicity is poorly understood, however several mechanisms have been suggested, including Hb extravasation across the blood vessel wall, scavenging of endothelial nitric oxide (NO), oversupply of oxygen, and heme-mediated oxidative side reactions. Although there are some in vitro and limited animal studies supporting these mechanisms, heme mediated reactivity appears to provide an alternative path that can explain some of the observed pathophysiological changes. Moreover, recent mechanistic and animal studies support a role for globin and heme scavengers in controlling oxidative toxicity associated with Hb infusion.

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“…N 2 O 3 does not react with the ferrous heme and is freely diffusible. Basu and colleagues detected the intermediate metHb-nitrite during the reaction of nitrite with deoxyHb and proposed that this intermediate may react rapidly with NO to form N 2 O 3 , a nitrosylating species (Basu et al , 2007; Roche et al , 2013). One caveat of this reaction is that metHb-nitrite must outcompete any surrounding Hb for NO, therefore, compartmentalization of this reaction may be necessary for it to play a physiological role.…”

Section: N2o3mentioning

confidence: 99%

“…Friedman and coworkers have suggested that a N 2 O 3 bound Hb species forms during the reaction of metHb and nitrite. They detected the formation of an intermediate capable of S-nitrosation and GSNO formation under multiple conditions when metHb, NO, and nitrite were mixed (Roche et al , 2013). Also, the addition of reducing agent L-cysteine to metHb and nitrite reduced a small population of metHb to deoxyHb.…”

Section: N2o3mentioning

confidence: 99%

Recent insights into nitrite signaling processes in blood

Helms

Liu

Kim‐Shapiro

2016

Biological Chemistry

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Nitrite was once thought to be inert in human physiology. However, research over the past few decades has established a link between nitrite and the production of nitric oxide (NO) that is potentiated under hypoxic and acidic conditions. Under this new role nitrite acts as a storage pool for bioavailable NO. The NO so produced is likely to play important roles in decreasing platelet activation, contributing to hypoxic vasodilation, and minimizing blood-cell adhesion to endothelial cells. Researchers have proposed multiple mechanisms for nitrite reduction in the blood. However, NO production in blood must somehow overcome rapid scavenging by hemoglobin in order to be effective. Here we review the role of red blood cell hemoglobin in the reduction of nitrite and present recent research into mechanisms that may allow nitric oxide and other reactive nitrogen signaling species to escape the red blood cell.

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Generating S-Nitrosothiols from Hemoglobin

Cited by 28 publications

References 99 publications

Bio‐inspired nanomedicine strategies for artificial blood components

Bio‐inspired nanomedicine strategies for artificial blood components

Blood substitutes: why haven’t we been more successful?

Recent insights into nitrite signaling processes in blood

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