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Environment International Mar 2019The widespread occurrence and adverse environmental and health-related impacts of various types of emerging contaminants (ECs) have become an issue of high concern. With... (Review)
Review
The widespread occurrence and adverse environmental and health-related impacts of various types of emerging contaminants (ECs) have become an issue of high concern. With ever increasing scientific knowledge, socio-economic awareness, health-related problems and ecological apprehensions, people are more concerned about the widespread ECs, around the globe. Among ECs, biologically active compounds from pharmaceutical, cosmeceutical, biomedical, personal care products (PPCPs), endocrine-disrupting chemicals (EDCs), and flame-retardants are of paramount concern. The presence and persistence of ECs in water bodies are of continued and burning interest, worldwide. Various types of ECs are being discharged knowingly/unknowingly with/without partial treatments into the aquatic environments that pose serious health issues and affects the entire living ecosystem. So far, various approaches have been developed for ECs degradation and removal to diminish their adverse impact. Many previous and/or ongoing studies have focused on contaminants degradation and efficient removal via numerous treatment strategies, i.e. (1) physical, (2) chemical and (3) biological. However, the experimental evidence is lacking to enable specific predictions about ECs mechanistic degradation and removal fate across various in-practice systems. In this context, the deployment oxidoreductases such as peroxidases (lignin peroxidases, manganese-dependent peroxidases, and horseradish peroxidase), aromatic dioxygenases, various oxygenases, laccases, and tyrosinases have received considerable research attention. Immobilization is highlighted as a promising approach to improve enzyme catalytic performance and stabilization, as well as, to protect the three-dimensional structure of the enzyme against the undesirable consequences of harsh reaction environment. This work overviews the current and state-of-the-art critical aspect related to hazardous pollutants at large and ECs in particular by the immobilized oxidoreductase enzymes. The first part of the review focuses on the occurrence, physiochemical behavior, potent sources and significant routes of ECs. Following that, environmentally-related adverse impacts and health-related issues of ECs are discussed in the second part. In the third part, biodegradation and removal strategies with a comparative overview of several conventional vs. non-conventional methods are presented briefly. The fourth part majorly focuses on operational modes of different oxidoreductase enzyme-based biocatalytic processes for the biodegradation and biotransformation of a wide array of harmful environmental contaminants. Finally, the left behind research gaps, concluding remarks as well as future trends and recommendations in the use of carrier-immobilized oxidoreductases for environmental perspective are also discussed.
Topics: Animals; Biodegradation, Environmental; Ecosystem; Environmental Pollutants; Humans; Oxidoreductases
PubMed: 30660847
DOI: 10.1016/j.envint.2019.01.011 -
Molecules (Basel, Switzerland) May 2023A story going back almost 40 years is presented in this manuscript. This is a different and more challenging way of reporting my research and I hope it will be useful to... (Review)
Review
A story going back almost 40 years is presented in this manuscript. This is a different and more challenging way of reporting my research and I hope it will be useful to and target a wide-ranging audience. When preparing the manuscript and collecting references on the subject of this paper-aldehyde oxidoreductase from -I felt like I was travelling back in time (and space), bringing together the people that have contributed most to this area of research. I sincerely hope that I can give my collaborators the credit they deserve. This study is not presented as a chronologic narrative but as a grouping of topics, the development of which occurred over many years.
Topics: Humans; Aldehyde Oxidoreductases; Desulfovibrio gigas; Desulfovibrio; Molybdenum; Aldehyde Dehydrogenase
PubMed: 37241969
DOI: 10.3390/molecules28104229 -
Environmental Health Perspectives Oct 1998Acute lung injury represents a wide spectrum of pathologic processes, the most severe end of the spectrum being the acute respiratory distress syndrome. Reactive oxygen... (Review)
Review
Acute lung injury represents a wide spectrum of pathologic processes, the most severe end of the spectrum being the acute respiratory distress syndrome. Reactive oxygen intermediates have been implicated as important in the pathobiochemistry of acute lung injury. The endogenous sources that contribute to the generation of reactive oxygen intermediates in acute lung injury are poorly defined but probably include the molybdenum hydroxylases, NAD(P)H oxidoreductases, the mitochondrial electron transport chain, and arachidonic acid-metabolizing enzymes. Our laboratory has focused, in particular, on the regulation of two of these enzyme systems, xanthine oxidoreductase (XDH/XO) and NAD(P)H oxidase. We observe that gene expression of XDH/XO is regulatory in a cell-specific manner and is markedly affected by inflammatory cytokines, steroids, and physiologic events such as hypoxia. Posttranslational processing is also important in regulating XDH/XO activity. More recently, the laboratory has characterized an NAD(P)H oxidase in vascular cells. The cytochrome components of the oxidase, gp91 and p22, appear similar to the components present in phagocytic cells that contribute to their respiratory burst. In human vascular endothelial and smooth muscle cells, oncostatin M potently induces gp91 expression. We believe that regulation of gp91 is a central controlling factor in expression of the vascular NAD(P)H oxidase. In summary, the studies support the concept that the oxidoreductases of vascular cells are expressed in a highly regulated and self-specific fashion.
Topics: Animals; Blood Vessels; Gene Expression Regulation, Enzymologic; Humans; Lung; Lung Injury; NADH, NADPH Oxidoreductases; Oxidants; Oxidoreductases; Xanthine Dehydrogenase; Xanthine Oxidase
PubMed: 9788904
DOI: 10.1289/ehp.98106s51235 -
Experimental Biology and Medicine... Mar 2015The WW domain-containing oxidoreductase (WWOX) encodes a tumor suppressor that is frequently altered in cancer. WWOX binds several proteins and thus is postulated to be... (Review)
Review
The WW domain-containing oxidoreductase (WWOX) encodes a tumor suppressor that is frequently altered in cancer. WWOX binds several proteins and thus is postulated to be involved in a variety of cellular processes. Interestingly, Wwox-knockout mice develop normally in utero but succumb to hypoglycemia and other metabolic defects early in life resulting in their death by 3-4 weeks of age. Cumulative evidence has linked WWOX with cellular metabolism including steroid metabolism, high-density lipoprotein cholesterol (HDL-C) metabolism, bone metabolism and, more recently, glucose metabolism. In this review, we discuss these evolving functions for WWOX and how its deletion affects cellular metabolism and neoplastic progression.
Topics: Animals; Bone and Bones; Cells; Cholesterol, HDL; Disease Models, Animal; Disease Progression; Glucose; Humans; Mice; Mice, Knockout; Neoplasms; Oxidoreductases; Steroids; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 25491415
DOI: 10.1177/1535370214561956 -
Experimental Biology and Medicine... Mar 2015WWOX, the WW domain-containing oxidoreductase gene at chromosome region 16q23.3-q24.1, spanning chromosomal fragile site FRA16D, encodes the 46 kDa Wwox protein, a... (Review)
Review
WWOX, the WW domain-containing oxidoreductase gene at chromosome region 16q23.3-q24.1, spanning chromosomal fragile site FRA16D, encodes the 46 kDa Wwox protein, a tumor suppressor that is lost or reduced in expression in a wide variety of cancers, including breast, prostate, ovarian, and lung. The function of Wwox as a tumor suppressor implies that it serves a function in the prevention of carcinogenesis. Indeed, in vitro studies show that Wwox protein interacts with many binding partners to regulate cellular apoptosis, proliferation, and/or maturation. It has been reported that newborn Wwox knockout mice exhibit nascent osteosarcomas while Wwox(+/-) mice exhibit increased incidence of spontaneous and induced tumors. Furthermore, absence or reduction of Wwox expression in mouse xenograft models results in increased tumorigenesis, which can be rescued by Wwox re-expression, though there is not universal agreement among investigators regarding the role of Wwox loss in these experimental models. Despite this proposed tumor suppressor function, the overlap of the human WWOX locus with FRA16D sensitizes the gene to protein-inactivating deletions caused by replication stress. The high frequency of deletions within the WWOX locus in cancers of various types, without the hallmark protein inactivation-associated mutations of "classical" tumor suppressors, has led to the proposal that WWOX deletions in cancers are passenger events that occur in early cancer progenitor cells due to fragility of the genetic locus, rather than driver events which provide the cancer cell a selective advantage. Recently, a proposed epigenetic cause of chromosomal fragility has suggested a novel mechanism for early fragile site instability and has implications regarding the involvement of tumor suppressor genes at chromosomal fragile sites in cancer. In this review, we provide an overview of the evidence for WWOX as a tumor suppressor gene and put this into the context of fragility associated with the FRA16D locus.
Topics: Animals; Carcinogenesis; Chromosome Fragile Sites; Disease Models, Animal; Humans; Mice; Mutation; Oxidoreductases; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 25538133
DOI: 10.1177/1535370214561590 -
Experimental Biology and Medicine... Mar 2015Human fragile WWOX gene encodes a tumor suppressor WW domain-containing oxidoreductase (named WWOX, FOR, or WOX1). Functional suppression of WWOX prevents apoptotic cell... (Review)
Review
Human fragile WWOX gene encodes a tumor suppressor WW domain-containing oxidoreductase (named WWOX, FOR, or WOX1). Functional suppression of WWOX prevents apoptotic cell death induced by a variety of stress stimuli, such as tumor necrosis factor, UV radiation, and chemotherapeutic drug treatment. Loss of WWOX gene expression due to gene deletions, loss of heterozygosity, chromosomal translocations, or epigenetic silencing is frequently observed in human malignant cancer cells. Acquisition of chemoresistance in squamous cell carcinoma, osteosarcoma, and breast cancer cells is associated with WWOX deficiency. WWOX protein physically interacts with many signaling molecules and exerts its regulatory effects on gene transcription and protein stability and subcellular localization to control cell survival, proliferation, differentiation, autophagy, and metabolism. In this review, we provide an overview of the recent advances in understanding the molecular mechanisms by which WWOX regulates cellular functions and stress responses. A potential scenario is that activation of WWOX by anticancer drugs is needed to overcome chemoresistance and trigger cancer cell death, suggesting that WWOX can be regarded as a prognostic marker and a candidate molecule for targeted cancer therapies.
Topics: Apoptosis; Drug Resistance, Neoplasm; Humans; Neoplasms; Oxidoreductases; Signal Transduction; Stress, Physiological; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 25595191
DOI: 10.1177/1535370214566747 -
Experimental Biology and Medicine... Mar 2015WWOX is a gene that spans an extremely large chromosomal region. It is derived from within chromosomal band 16q23.2 which is a region with frequent deletions and other... (Review)
Review
WWOX is a gene that spans an extremely large chromosomal region. It is derived from within chromosomal band 16q23.2 which is a region with frequent deletions and other alterations in a variety of different cancers. This chromosomal band also contains the FRA16D common fragile site (CFS). CFSs are chromosomal regions found in all individuals which are highly unstable. WWOX has also been demonstrated to function as a tumor suppressor that is involved in the development of many cancers. Two other highly unstable CFSs, FRA3B (3p14.2) and FRA6E (6q26), also span extremely large genes, FHIT and PARK2, respectively, and these two genes are also found to be important tumor suppressors. There are a number of interesting similarities between these three large CFS genes. In spite of the fact that they are derived from some of the most unstable chromosomal regions in the genome, they are found to be highly evolutionarily conserved and the chromosomal region spanning the mouse homologs of both WWOX and FHIT are also CFSs in mice. Many of the other CFSs also span extremely large genes and many of these are very attractive tumor suppressor candidates. WWOX is therefore a member of a very interesting family of very large CFS genes.
Topics: Animals; Carcinogenesis; Chromosome Fragile Sites; Disease Models, Animal; Genomic Instability; Humans; Mice; Neoplasms; Oxidoreductases; Signal Transduction; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 25595185
DOI: 10.1177/1535370214565992 -
Biochemical Society Transactions Jun 2012The study of natural enzymes is complicated by the fact that only the most recent evolutionary progression can be observed. In particular, natural oxidoreductases stand... (Review)
Review
The study of natural enzymes is complicated by the fact that only the most recent evolutionary progression can be observed. In particular, natural oxidoreductases stand out as profoundly complex proteins in which the molecular roots of function, structure and biological integration are collectively intertwined and individually obscured. In the present paper, we describe our experimental approach that removes many of these often bewildering complexities to identify in simple terms the necessary and sufficient requirements for oxidoreductase function. Ours is a synthetic biology approach that focuses on from-scratch construction of protein maquettes designed principally to promote or suppress biologically relevant oxidations and reductions. The approach avoids mimicry and divorces the commonly made and almost certainly false ascription of atomistically detailed functionally unique roles to a particular protein primary sequence, to gain a new freedom to explore protein-based enzyme function. Maquette design and construction methods make use of iterative steps, retraceable when necessary, to successfully develop a protein family of sturdy and versatile single-chain three- and four-α-helical structural platforms readily expressible in bacteria. Internally, they prove malleable enough to incorporate in prescribed positions most natural redox cofactors and many more simplified synthetic analogues. External polarity, charge-patterning and chemical linkers direct maquettes to functional assembly in membranes, on nanostructured titania, and to organize on selected planar surfaces and materials. These protein maquettes engage in light harvesting and energy transfer, in photochemical charge separation and electron transfer, in stable dioxygen binding and in simple oxidative chemistry that is the basis of multi-electron oxidative and reductive catalysis.
Topics: Oxidation-Reduction; Oxidoreductases; Protein Engineering; Recombinant Proteins; Synthetic Biology
PubMed: 22616867
DOI: 10.1042/BST20120067 -
Hormone Research 2008P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder of steroidogenesis with multiple clinical manifestations. POR is the electron donor for all... (Review)
Review
P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder of steroidogenesis with multiple clinical manifestations. POR is the electron donor for all microsomal P450 enzymes, including the three steroidogenic enzymes P450c17 (17alpha-hydroxylase/17,20-lyase), P450c21 (21-hydroxylase), and P450aro (aromatase). Since the first description of POR mutations in 2004, about 50 patients have been reported. Serum steroid profiles indicate partial deficiencies in 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase. The 17-OH progesterone levels are elevated, as in 21-hydroxylase deficiency, while androgen levels are low; cortisol may be normal but is poorly responsive to adrenocorticotropic hormone. Most patients also have associated skeletal malfor- mations (craniosynostosis, radio-ulnar synostosis, midface hypoplasia, bowed femora) termed Antley-Bixler syndrome. Antley-Bixler syndrome with normal steroidogenesis is caused by autosomal dominant gain-of-function mutations in fibroblast growth factor receptor 2. Males with POR deficiency are often undervirilized, while females can be virilized. The prognosis for patients with POR deficiency appears to depend on the severity of the bony malformations and their timely treatment. The potential impact of POR mutations on drug metabolism by other hepatic P450 enzymes requires further investigation. Given the varied physical and biochemical phenotype of POR deficiency and the risk of adrenal insufficiency, clinicians should be alert to this potential diagnosis.
Topics: Abnormalities, Multiple; Bone and Bones; Cytochrome P-450 Enzyme System; Endocrine System Diseases; Humans; Hydroxysteroid Dehydrogenases; Models, Biological; NADH, NADPH Oxidoreductases; Steroid 17-alpha-Hydroxylase; Steroid 21-Hydroxylase; Syndrome
PubMed: 18259105
DOI: 10.1159/000114857 -
Experimental Biology and Medicine... Mar 2015WWOX was cloned as a tumor suppressor gene mapping to chromosomal fragile site FRA16D. Loss of WWOX is closely related to tumorigenesis, cancer progression, and therapy... (Review)
Review
WWOX was cloned as a tumor suppressor gene mapping to chromosomal fragile site FRA16D. Loss of WWOX is closely related to tumorigenesis, cancer progression, and therapy resistance. Recent studies demonstrate the growing role of WWOX gene in other human pathologies such as metabolic and nervous system-related conditions. The neurologic phenotype of WWOX mutation includes seizures, ataxia, developmental delay, and spasticity of variable severity. WWOX is a ubiquitous protein with high expression in many tissues including brain, cerebellum, brain stem, and spinal cord. WWOX is highly expressed in different brain regions during murine fetal development and remained unchanged in the cortex and the corpus callosum in adult mice. The mechanism or the putative role of WWOX in the nervous system is still unclear but may include abnormal signaling protein, disruption of neuronal pathways, neuronal differentiation, mitochondrial dysfunction, or apoptosis. Homozygous mutations affecting WWOX in humans are likely to be more described in the future using exome sequencing. The described findings highlight that WWOX plays a critical role in normal central nervous system development and disease. The aim of this review is to summarize the roles of WWOX in the developing brain.
Topics: Animals; Brain; Brain Diseases; Chromosome Fragile Sites; Disease Models, Animal; Gene Expression Regulation, Developmental; Humans; Mice; Mutation; Oxidoreductases; Phenotype; Rats; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 25416187
DOI: 10.1177/1535370214561952