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heme review

Caroline C Philpott, Shyamalagauri Jadhav
Mammalian cells contain thousands of metalloproteins and have evolved sophisticated systems for ensuring that metal cofactors are correctly assembled and delivered to their proper destinations. Equally critical in this process are the strategies to avoid the insertion of the wrong metal cofactor into apo-proteins and to avoid the damage that redox-active metals can catalyze in the cellular milieu. Iron and zinc are the most abundant metal cofactors in cells and iron cofactors include heme, iron-sulfur clusters, and mono- and dinuclear iron centers...
October 12, 2018: Free Radical Biology & Medicine
Yirui Guo, Michael A Marletta
Heme-nitric oxide/oxygen binding (H-NOX) proteins are a family of gas-binding hemoproteins that bind diatomic gas ligands such as nitric oxide (NO) and oxygen (O₂). In bacteria, H-NOXs are often associated with signaling partners, including histidine kinases (HKs), diguanylate cyclases (DGCs) or methyl-accepting chemotaxis proteins (MCPs), either as a stand-alone protein or as a domain of a larger polypeptide. H-NOXs regulate the activity of cognate signaling proteins through ligand-induced conformational changes in the H-NOX domain and protein/protein interactions between the H-NOX and the cognate signaling partner...
October 15, 2018: Chembiochem: a European Journal of Chemical Biology
Tohru Fujiwara
Sideroblastic anemias (SAs) are heterogeneous congenital and acquired disorders characterized by anemia and the presence of ring sideroblasts in bone marrow. Congenital sideroblastic anemia (CSA) is a rare disease caused by mutations in genes that are involved in heme biosynthesis, iron-sulfur [Fe-S] cluster biosynthesis, and mitochondrial protein synthesis. The most common form of CSA is X-linked sideroblastic anemia; it occurs because of mutations in the erythroid-specific δ-aminolevulinate synthase gene (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Irina I Vlasova
The heme in the active center of peroxidases reacts with hydrogen peroxide to form highly reactive intermediates, which then oxidize simple substances called peroxidase substrates. Human peroxidases can be divided into two groups: (1) True peroxidases are enzymes whose main function is to generate free radicals in the peroxidase cycle and (pseudo)hypohalous acids in the halogenation cycle. The major true peroxidases are myeloperoxidase, eosinophil peroxidase and lactoperoxidase. (2) Pseudo-peroxidases perform various important functions in the body, but under the influence of external conditions they can display peroxidase-like activity...
October 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Lovisa Svensson, Mirjana Poljakovic, Isak Demirel, Charlotte Sahlberg, Katarina Persson
Urinary tract infection (UTI) is one of the most common bacterial infections in humans, and the majority are caused by uropathogenic Escherichia coli (UPEC). The rising antibiotic resistance among UPEC and the frequent failure of antibiotics to effectively treat recurrent UTI and catheter-associated UTI motivate research on alternative ways of managing UTI. Abundant evidence indicates that the toxic radical nitric oxide (NO), formed by activation of the inducible nitric oxide synthase, plays an important role in host defence to bacterial infections, including UTI...
2018: Advances in Microbial Physiology
Veronica Fiorito, Deborah Chiabrando, Emanuela Tolosano
Mitochondrial dysfunction has achieved an increasing interest in the field of neurodegeneration as a pathological hallmark for different disorders. The impact of mitochondria is related to a variety of mechanisms and several of them can co-exist in the same disease. The central role of mitochondria in neurodegenerative disorders has stimulated studies intended to implement therapeutic protocols based on the targeting of the distinct mitochondrial processes. The review summarizes the most relevant mechanisms by which mitochondria contribute to neurodegeneration, encompassing therapeutic approaches...
September 18, 2018: Pharmaceuticals
Azar Shokri, Mahdi Fakhar, Saeed Emami, Pooria Gill, Javad Akhtari
AIM AND BACKGROUND: Azoles as antifungal drugs, has been used to treat leishmaniasis for many years. Several evidences suggesting that the primary target of azoles is the heme protein, which cocatalyzes cytochrome P-450-dependent 14α-demethylation of lanosterol. Little is known about the structural changes caused by azoles with atomic force microscopy (AFM) or scanning electron microscopy (SEM). In the current work several patented antileishmanial agents reviewed (US8809555) (US 0269803 A1) (TW201802093 A)...
September 18, 2018: Recent Patents on Anti-infective Drug Discovery
D A Stoyanovsky, Y Y Tyurina, I Shrivastava, I Bahar, V A Tyurin, O Protchenko, S Jadhav, S B Bolevich, A V Kozlov, Y A Vladimirov, A A Shvedova, C C Philpott, H Bayir, V E Kagan
Duality of iron as an essential cofactor of many enzymatic metabolic processes and as a catalyst of poorly controlled redox-cycling reactions defines its possible biological beneficial and hazardous role in the body. In this review, we discuss these two "faces" of iron in a newly conceptualized program of regulated cell death, ferroptosis. Ferroptosis is a genetically programmed iron-dependent form of regulated cell death driven by enhanced lipid peroxidation and insufficient capacity of thiol-dependent mechanisms (glutathione peroxidase 4, GPX4) to eliminate hydroperoxy-lipids...
September 12, 2018: Free Radical Biology & Medicine
Mateusz Tomczyk, Izabela Kraszewska, Jozef Dulak, Agnieszka Jazwa-Kusior
Upon myocardial infarction (MI) immune system becomes activated by extensive necrosis of cardiomyocytes releasing intracellular molecules called damage-associated molecular patterns. Overactive and prolonged immune responses are likely to be responsible for heart failure development and progression in patients surviving the ischemic episode. Heme oxygenase-1 (HO-1) plays a crucial role in heme degradation and in this way releases carbon monoxide, free iron, and biliverdin. This stress-inducible enzyme is induced by various oxidative and inflammatory signals...
September 10, 2018: Vascular Pharmacology
Luisa B Maia, José J G Moura
Nitric oxide radical (NO) is a signaling molecule involved in several physiological and pathological processes and a new nitrate-nitrite-NO pathway has emerged as a physiological alternative to the "classic" pathway of NO formation from L-arginine. Since the late 1990s, it has become clear that nitrite can be reduced back to NO under hypoxic/anoxic conditions and exert a significant cytoprotective action in vivo under challenging conditions. To reduce nitrite to NO, mammalian cells can use different metalloproteins that are present in cells to perform other functions, including several heme proteins and molybdoenzymes, comprising what we denominated as the "non-dedicated nitrite reductases"...
October 2018: Redox Biology
Qi Xiao, Tianming Chen, Shilin Chen
Cancer is a leading cause of cases of mortality worldwide. The most effective method to cure solid tumors is surgery. Every year, >50% of cancer patients receive surgery to remove solid tumors. Surgery may increase the cure rate of most solid tumors by 4-11 fold. Surgery has many challenges, including identifying small lesions, locating metastases and confirming complete tumor removal. Fluorescence guidance describes a new approach to improve surgical accuracy. Near-infrared fluorescence imaging allows for real-time early diagnosis and intraoperative imaging of lesion tissue...
September 2018: Experimental and Therapeutic Medicine
Simon P Ojolo, Shijiang Cao, S V G N Priyadarshani, Weimin Li, Maokai Yan, Mohammad Aslam, Heming Zhao, Yuan Qin
In eukaryotes, genetic material is packaged into a dynamic but stable nucleoprotein structure called chromatin. Post-translational modification of chromatin domains affects the expression of underlying genes and subsequently the identity of cells by conveying epigenetic information from mother to daughter cells. SWI/SNF chromatin remodelers are ATP-dependent complexes that modulate core histone protein polypeptides, incorporate variant histone species and modify nucleotides in DNA strands within the nucleosome...
2018: Frontiers in Plant Science
Nitika Singh, Abhishek Kumar, Vivek Kumar Gupta, Bechan Sharma
The effects of lead exposure on mammals are reported to be devastating. Lead is present in all the abiotic environmental components such as brass, dust, plumbing fixtures, soil, water, and lead mixed imported products. Its continuous use for several industrial and domestic purposes has caused a rise in its levels, thereby posing serious threats to human health. The mechanisms involved in lead-induced toxicity primarily include free-radical-mediated generation of oxidative stress which directly imbalances the prooxidants and the antioxidants in body...
September 17, 2018: Chemical Research in Toxicology
Qian-Qian Li, Lan-Jun Li, Xin-Yu Wang, Yu-Ying Sun, Jun Wu
Intracerebral hemorrhage (ICH) is a fatal acute cerebrovascular disease, with a high morbidity and mortality. Following ICH, erythrocytes release heme and several of its metabolites, thereby contributing to brain edema and secondary brain damage. Heme oxygenase is the initial and rate-limiting enzyme of heme catabolism, and the expression of heme oxygenase-1 (HO-1) is rapidly induced following acute brain injury. As HO-1 exerts it effects via various metabolites, its role during ICH remains complex. Therefore, in-depth studies regarding the role of HO-1 in secondary brain damage following ICH may provide a theoretical basis for neuroprotective function after ICH...
2018: Frontiers in Neurology
Shaowei Li, Masayuki Fujino, Terumi Takahara, Xiao-Kang Li
Ischemia-reperfusion (IR) injury is a kind of injury resulting from the restoration of the blood supply after blood vessel closure during liver transplantation and is the main cause of graft failure. The pathophysiological mechanisms of hepatic IR include a variety of oxidative stress responses. Hepatic IR is characterized by ischemia and hypoxia inducing oxidative stress, immune response and apoptosis. Fat-denatured livers are also used as donors due to the lack of liver donors. Fatty liver is less tolerant to IR than normal liver...
August 31, 2018: Medical Molecular Morphology
Cheng-Peng Yu, Shu-Fang Fu, Xuan Chen, Jing Ye, Yuan Ye, Ling-Dong Kong, Zhengming Zhu
BACKGROUND/AIMS: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme catalyzing the initial and rate-limiting steps in the kynurenine pathway, which converts tryptophan into kynurenine. Upregulation of IDO1 decreases tryptophan levels and increases the accumulation of kynurenine and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence has shown that IDO1 is highly expressed in various cancer types and associated with poor prognosis of cancer patients...
2018: Cellular Physiology and Biochemistry
Abdisamad M Ibrahim, Sukesh Manthri, Paolo K Soriano, Vikrampal Bhatti, Chaitanya K Mamillapalli
Influenza A associated with rhabdomyolysis has become more commonly recognized in recent years. It requires prompt recognition and treatment in order to prevent heme pigment-induced acute kidney injury. Here we report a 50-year-old female without a significant past medical history who presented with a one-week history of fevers, chills, fatigue, and generalized body aches. She was on no prior medication. Laboratory studies were significant for leukocytosis and elevated creatinine kinase up to a peak of 28,216 IU/L...
June 11, 2018: Curēus
Nicholas Heming, Sivanthiny Sivanandamoorthy, Paris Meng, Rania Bounab, Djillali Annane
Sepsis, a life-threatening organ dysfunction, results from a dysregulated host response to invading pathogens that may be characterized by overwhelming systemic inflammation or some sort of immune paralysis. Sepsis remains a major cause of morbidity and mortality. Treatment is nonspecific and relies on source control and organ support. Septic shock, the most severe form of sepsis is associated with the highest rate of mortality. Two large multicentre trials, undertaken 15 years apart, found that the combination of hydrocortisone and fludrocortisone significantly reduces mortality in septic shock...
2018: Frontiers in Immunology
Tohru Fujiwara, Hideo Harigae
Sideroblastic anemia is a heterogeneous congenital and acquired disorder characterized by anemia and the presence of ring sideroblasts in the bone marrow. Congenital sideroblastic anemia (CSA) is a rare disease caused by mutations in genes involved in the heme biosynthesis, iron-sulfur [Fe-S] cluster biosynthesis, and mitochondrial protein synthesis. The most prevalent form of CSA is X-linked sideroblastic anemia, caused by mutations in the erythroid-specific δ-aminolevulinate synthase (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells...
August 8, 2018: Free Radical Biology & Medicine
Rebecca K Donegan, Courtney M Moore, David A Hanna, Amit R Reddi
Heme is an essential cofactor and signaling molecule required for virtually all aerobic life. However, excess heme is cytotoxic. Therefore, heme must be safely transported and trafficked from the site of synthesis in the mitochondria or uptake at the cell surface, to hemoproteins in most subcellular compartments. While heme synthesis and degradation are relatively well characterized, little is known about how heme is trafficked and transported throughout the cell. Herein, we review eukaryotic heme transport, trafficking, and mobilization, with a focus on factors that regulate bioavailable heme...
August 6, 2018: Free Radical Biology & Medicine
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