a(MESH:"Reactive Oxygen Species")
Heme activates neutrophils and endothelial cells, by ROS generation. PubMed:24904418
ROS generation by haem is at least partially dependent on the Fenton reaction, in which iron catalyses the production of toxic ROS (Wagener et al, 2003). PubMed:25307023
Protein tyrosine nitration has been identified as a biomarker of oxidative stress, and the generation of 3-nitrotyrosine (3-NT) is often accompanied with the increasing of ROS and RNS under pathologic condition [14]. PubMed:30324533
As expected, α-tocopherol treatment prevented ROS accumulation and the induction of anti-oxidant genes in the heart (Figure 6A, B and see Figure 8 in [37]). PubMed:28400318
We confirmed that the redox active iron, which is derived from heme catabolism in macrophages, is capable of catalyzing ROS formation (Fig. 7A) (19). PubMed:29212341
We showed that NAC treatment scavenged ROS production and, more importantly, it counteracted ferroportin induction by heme (Fig. 8B, C). PubMed:29212341
Corroborating recent studies that showed heme as an inductor of ROS generation via NADPHox in neutrophils, macrophages and in VSMC [7,8,19], the pretreatment of cells with DPI (10 mM), a NADPHox inhibitor [20], prevented heme-induced ROS production in A7r5 VSMC (Fig. 2A). PubMed:22954673
Accordingly, Fig. 2A shows that heme (10 mM) induces a strong ROS production after 1 h of incubation with VSMC. PubMed:22954673
Corroborating recent studies that showed heme as an inductor of ROS generation via NADPHox in neutrophils, macrophages and in VSMC [7,8,19], the pretreatment of cells with DPI (10 mM), a NADPHox inhibitor [20], prevented heme-induced ROS production in A7r5 VSMC (Fig. 2A). PubMed:22954673
Furthermore, heme induces ROS generation dependent on enzymatic reactions. PubMed:24904418
Heme induces ROS generation independently of TLR4. PubMed:24904418
The main mediator of these adverse effects is thought to be free haem via its effects on NO scavenging, pro-inflammatory cytokine responses, and reactive oxygen species (ROS) generation. PubMed:25307023
In addition, we observed increased ROS production ( Figure 2I; supplemental Figure 2), as well as an enhanced expression of IL-6 and TNFα in cells treated with heme-albumin compared with heme-Hx (Figure 2J-K). PubMed:26675351
Toxicity of free hemoglobin is also caused by the release of cell-free heme, which produces lipid peroxidation and mitochondrial damage and increases the production of reactive oxygen species. PubMed:27515135
Heme is an amphipathic molecule that can promote the generation of reactive oxygen species (ROS) via Fenton chemistry, thereby leading to membrane damage. PubMed:27798618
Moreover, heme-derived ROS induce the proliferation of smooth muscle cells, that participate in vasculopathy associated with atherosclerosis and hypertension [15]. PubMed:28400318
Free heme upregulates heme oxygenase activity, generates reactive oxygen species, and activates endothelial cells and macrophages directly[65]. PubMed:28458720
As expected, incubation of neutrophils with hemin resulted in a significant number of cells producing ROS (Fig. 8A and B). PubMed:28716864
For instance, earlier studies have demonstrated that neutrophil elastase degrades the hemoglobin liberating free hemin that induces ROS production. PubMed:28716864
We show that heme, in a concentration range found during hemolytic episodes, increases intracellular ROS production and consequentially signals for ferroportin induction and subsequent iron export from the macrophages. PubMed:29212341
By contrast, treatment of macrophages with PPIX failed to increase the ROS production and ferroportin expression, implying that iron within the heme moiety was required for the observed effects (Fig. 7B). PubMed:29212341
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, cytokine secretion depends on the coordinated iron in the porphyrin ring (Figueiredo et al, 2007), and nuclear factor-jB (NF-jB), MAPKs activation and ROS are essential for the increase in cytokine production induced by haem (Fernandez et al, 2010). PubMed:25307023
Although neutrophils have important functions controlling infection, these cells can promote vascular and tissue injury by generating ROS, secreting proteases, and releasing extracellular chromatin (NETs; reviewed in Mócsai, 2013). PubMed:24904418
As a part of the inflammatory response after injury, oxidative stress due to formation of reactive oxygen species (ROS) is involved both in direct damage of cartilage components and as integral factors in cell signaling leading to cartilage degradation (Henrotin et al., 2003). PubMed:30505280
The role of PRDX2 in inhibiting impaired deformability can be attributed to both a reduction in ROS as well as a direct reaction of PRDX2 with protein hydroperoxides [52], which will inhibit the damage to cytoskeletal proteins required for impaired deformability. PubMed:23215741
Apoptosis has been found to be a major rout for the elimination of cells after a variety of stresses including ROS and RNS [30]. PubMed:30324533
Taken together, these data demonstrate that Hx limits macrophage heme overload and prevents the prooxidant and proinflammatory effects triggered by heme in cellular assays and in vivo. PubMed:26675351
Importantly, by scavenging free heme, Hx prevents heme-induced M1 macrophage polarization and thus avoids both TLR4 activation and ROS formation. PubMed:26675351
Being heme a well-known pro-oxidant agent [17], we then evaluated ROS levels in CMs exposed to heme alone or bound to either Hx or albumin. In the presence of Hx-heme complexes, CMs were protected from ROS formation, if compared to CMs treated with either albumin-heme complexes or heme alone (Figure 1D). PubMed:28400318
The ability of hemin to trigger ROS production in neutrophils was abrogated significantly in the presence of A1AT (Fig. 8). PubMed:28716864
WhileMAPK8 increases ROS generation, TNF induces RIP1–RIP3 necrosome which triggers necroptosis. PubMed:24904418
The role of PRDX2 in inhibiting impaired deformability can be attributed to both a reduction in ROS as well as a direct reaction of PRDX2 with protein hydroperoxides [52], which will inhibit the damage to cytoskeletal proteins required for impaired deformability. PubMed:23215741
The expression of A1M is up-regulated by elevated levels of free Hb, heme and ROS [23]. PubMed:24489717
Expression and synthesis of A1M has been shown to be upregulated in cells after exposure to heme and ROS (Olsson et al., 2007, 2011). PubMed:30505280
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Mechanistically, heme-derived ROS may directly modify Ca2+ handling proteins (such as the RyR2 or SERCA2a) [35, 57], and may also activate intracellular stress kinases, such as CaMKII [58], which in turn phosphorylate the same Ca2+ effectors and ultimately exacerbate Ca2+ mishandling. PubMed:28400318
Additionally, it was observed that inhibition of HO-1 by ZnPP induced a further increase in hemeinduced ROS production (Fig. 4C), suggesting that activation of HO system attenuates the NADPHox-dependent activation of VSMC induced by heme. PubMed:22954673
Excess production of reactive oxygen species (ROS) has been implicated in progression of chronic heart failure as well as in other cardiovascular disorders including ischemia-reperfusion injury and cardiovascular complications of hemolytic diseases [2-7]. PubMed:28400318
Excess production of reactive oxygen species (ROS) has been implicated in progression of chronic heart failure as well as in other cardiovascular disorders including ischemia-reperfusion injury and cardiovascular complications of hemolytic diseases [2-7]. PubMed:28400318
Moreover, heme-derived ROS induce the proliferation of smooth muscle cells, that participate in vasculopathy associated with atherosclerosis and hypertension [15]. PubMed:28400318
Moreover, heme-derived ROS induce the proliferation of smooth muscle cells, that participate in vasculopathy associated with atherosclerosis and hypertension [15]. PubMed:28400318
. In the presence of reactive oxygen species (ROS), Hb is oxidized to methemoglobin (MetHb; Balla et al., 1993), characterized by the change in the oxidative state of the Fe present in the heme molecule from ferrous (Fe+2) to ferric (Fe+3). PubMed:24904418
Heme activates neutrophils and endothelial cells, by ROS generation. PubMed:24904418
The role of PRDX2 in inhibiting impaired deformability can be attributed to both a reduction in ROS as well as a direct reaction of PRDX2 with protein hydroperoxides [52], which will inhibit the damage to cytoskeletal proteins required for impaired deformability. PubMed:23215741
The role of PRDX2 in inhibiting impaired deformability can be attributed to both a reduction in ROS as well as a direct reaction of PRDX2 with protein hydroperoxides [52], which will inhibit the damage to cytoskeletal proteins required for impaired deformability. PubMed:23215741
The expression of A1M is up-regulated by elevated levels of free Hb, heme and ROS [23]. PubMed:24489717
Expression and synthesis of A1M has been shown to be upregulated in cells after exposure to heme and ROS (Olsson et al., 2007, 2011). PubMed:30505280
. In the presence of reactive oxygen species (ROS), Hb is oxidized to methemoglobin (MetHb; Balla et al., 1993), characterized by the change in the oxidative state of the Fe present in the heme molecule from ferrous (Fe+2) to ferric (Fe+3). PubMed:24904418
A seminal study demonstrated that the ability of heme to activate neutrophils depend on protein kinase C (PKC) activation and ROS generation, inducing the expression of adhesion molecules and modifying actin cytoskeleton dynamics, necessary features for neutrophils migration (Graça-Souza et al., 2002). PubMed:24904418
Although neutrophils have important functions controlling infection, these cells can promote vascular and tissue injury by generating ROS, secreting proteases, and releasing extracellular chromatin (NETs; reviewed in Mócsai, 2013). PubMed:24904418
However, ROS is necessary to induce TNF secretion and MAPK activation. PubMed:24904418
However, ROS is necessary to induce TNF secretion and MAPK activation. PubMed:24904418
Heme activates neutrophils and endothelial cells, by ROS generation. PubMed:24904418
The main mediator of these adverse effects is thought to be free haem via its effects on NO scavenging, pro-inflammatory cytokine responses, and reactive oxygen species (ROS) generation. PubMed:25307023
Toxicity of free hemoglobin is also caused by the release of cell-free heme, which produces lipid peroxidation and mitochondrial damage and increases the production of reactive oxygen species. PubMed:27515135
Heme is an amphipathic molecule that can promote the generation of reactive oxygen species (ROS) via Fenton chemistry, thereby leading to membrane damage. PubMed:27798618
As expected, incubation of neutrophils with hemin resulted in a significant number of cells producing ROS (Fig. 8A and B). PubMed:28716864
These ROS then oxidize cell membrane constituents to induce cytotoxicity and promote inflammation and thrombosis. PubMed:25307023
These ROS then oxidize cell membrane constituents to induce cytotoxicity and promote inflammation and thrombosis. PubMed:25307023
These ROS then oxidize cell membrane constituents to induce cytotoxicity and promote inflammation and thrombosis. PubMed:25307023
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, ROS induction by haem directly depends on signal transduction involving Ga inhibitory protein and phosphoinositide 3-kinase, and partially depends on phospholipase Cb, protein kinase C, the mitogen-activated protein kinases (MAPKs) and Rho kinase in neutrophils (Porto et al, 2007). PubMed:25307023
Furthermore, cytokine secretion depends on the coordinated iron in the porphyrin ring (Figueiredo et al, 2007), and nuclear factor-jB (NF-jB), MAPKs activation and ROS are essential for the increase in cytokine production induced by haem (Fernandez et al, 2010). PubMed:25307023
Platelets may be activated during haemolysis by several different mechanisms involving decreased NO levels, increased pro-inflammatory cytokines and mediators, and ROS. PubMed:25307023
Importantly, by scavenging free heme, Hx prevents heme-induced M1 macrophage polarization and thus avoids both TLR4 activation and ROS formation. PubMed:26675351
Excess production of reactive oxygen species (ROS) has been implicated in progression of chronic heart failure as well as in other cardiovascular disorders including ischemia-reperfusion injury and cardiovascular complications of hemolytic diseases [2-7]. PubMed:28400318
Excess production of reactive oxygen species (ROS) has been implicated in progression of chronic heart failure as well as in other cardiovascular disorders including ischemia-reperfusion injury and cardiovascular complications of hemolytic diseases [2-7]. PubMed:28400318
Moreover, heme-derived ROS induce the proliferation of smooth muscle cells, that participate in vasculopathy associated with atherosclerosis and hypertension [15]. PubMed:28400318
Moreover, heme-derived ROS induce the proliferation of smooth muscle cells, that participate in vasculopathy associated with atherosclerosis and hypertension [15]. PubMed:28400318
Moreover, heme-derived ROS induce the proliferation of smooth muscle cells, that participate in vasculopathy associated with atherosclerosis and hypertension [15]. PubMed:28400318
Mechanistically, heme-derived ROS may directly modify Ca2+ handling proteins (such as the RyR2 or SERCA2a) [35, 57], and may also activate intracellular stress kinases, such as CaMKII [58], which in turn phosphorylate the same Ca2+ effectors and ultimately exacerbate Ca2+ mishandling. PubMed:28400318
We showed that NAC treatment scavenged ROS production and, more importantly, it counteracted ferroportin induction by heme (Fig. 8B, C). PubMed:29212341
We show that heme, in a concentration range found during hemolytic episodes, increases intracellular ROS production and consequentially signals for ferroportin induction and subsequent iron export from the macrophages. PubMed:29212341
Apoptosis has been found to be a major rout for the elimination of cells after a variety of stresses including ROS and RNS [30]. PubMed:30324533
Protein tyrosine nitration has been identified as a biomarker of oxidative stress, and the generation of 3-nitrotyrosine (3-NT) is often accompanied with the increasing of ROS and RNS under pathologic condition [14]. PubMed:30324533
As a part of the inflammatory response after injury, oxidative stress due to formation of reactive oxygen species (ROS) is involved both in direct damage of cartilage components and as integral factors in cell signaling leading to cartilage degradation (Henrotin et al., 2003). PubMed:30505280
As a part of the inflammatory response after injury, oxidative stress due to formation of reactive oxygen species (ROS) is involved both in direct damage of cartilage components and as integral factors in cell signaling leading to cartilage degradation (Henrotin et al., 2003). PubMed:30505280
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.