scholarly journals Biological and clinical significance of haptoglobin polymorphism in humans

1996 ◽  
Vol 42 (10) ◽  
pp. 1589-1600 ◽  
Author(s):  
M R Langlois ◽  
J R Delanghe
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Diseases ◽  
Prostaglandin Synthesis ◽  
Genetic Fingerprint ◽  
Functional Differences ◽  
Hemoglobin Binding ◽  
Human Pathology ◽  
Clinical Consequences ◽  
Haptoglobin Polymorphism

Abstract Haptoglobin is a hemoglobin-binding protein expressed by a genetic polymorphism as three major phenotypes: 1-1, 2-1, and 2-2. Most attention has been paid to determining haptoglobin phenotype as a genetic fingerprint used in forensic medicine. More recently, several functional differences between haptoglobin phenotypes have been demonstrated that appear to have important biological and clinical consequences. Haptoglobin polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases, including infections, atherosclerosis, and autoimmune disorders. These effects are explained by a phenotype-dependent modulation of oxidative stress and prostaglandin synthesis. Recent evidence is growing that haptoglobin is involved in the immune response as well. The strong genetic pressure favoring the 2-2 phenotype suggests an important role of haptoglobin in human pathology.

scholarly journals Influence of Haptoglobin Polymorphism on Stroke in Sickle Cell Disease Patients

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 144
Author(s):  
Olivia Edwards ◽  
Alicia Burris ◽  
Josh Lua ◽  
Diana J. Wilkie ◽  
Miriam O. Ezenwa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Cells ◽  
Cell Disease ◽  
Free Hemoglobin ◽  
Cerebral Tissue ◽  
Sickle Hemoglobin ◽  
Haptoglobin Polymorphism

This review outlines the current clinical research investigating how the haptoglobin (Hp) genetic polymorphism and stroke occurrence are implicated in sickle cell disease (SCD) pathophysiology. Hp is a blood serum glycoprotein responsible for binding and removing toxic free hemoglobin from the vasculature. The role of Hp in patients with SCD is critical in combating blood toxicity, inflammation, oxidative stress, and even stroke. Ischemic stroke occurs when a blocked vessel decreases oxygen delivery in the blood to cerebral tissue and is commonly associated with SCD. Due to the malformed red blood cells of sickle hemoglobin S, blockage of blood flow is much more prevalent in patients with SCD. This review is the first to evaluate the role of the Hp polymorphism in the incidence of stroke in patients with SCD. Overall, the data compiled in this review suggest that further studies should be conducted to reveal and evaluate potential clinical advancements for gene therapy and Hp infusions.

scholarly journals Vitamin C Deficiency and Scurvy Are Not Only a Dietary Problem but Are Codetermined by the Haptoglobin Polymorphism

2007 ◽  
Vol 53 (8) ◽  
pp. 1397-1400 ◽  
Author(s):  
Joris R Delanghe ◽  
Michel R Langlois ◽  
Marc L De Buyzere ◽  
Mathieu A Torck
Keyword(s):  
Vitamin C ◽  
Ldl Oxidation ◽  
Long Distance ◽  
Vitamin C Deficiency ◽  
Asian Populations ◽  
Functional Differences ◽  
Clinical Consequences ◽  
Genetically Determined

Abstract Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype–related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis between Hp phenotypes is attributable to variation in LDL oxidation. The classical view of vitamin C and scurvy being a pure nutritional condition needs to be updated. These findings should foster research investigating the role of Hp polymorphism in human disease, and in vitamin C deficiency and atherosclerosis in particular.

scholarly journals The Role of Zinc and Copper in Gynecological Malignancies

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3732
Author(s):  
Kaja Michalczyk ◽  
Aneta Cymbaluk-Płoska
Keyword(s):  
Oxidative Stress ◽  
Trace Elements ◽  
Inflammatory Diseases ◽  
Antioxidant Properties ◽  
Compensatory Mechanisms ◽  
Gynecological Malignancies ◽  
Zn And Cu In ◽  
Enzymatic Systems ◽  
Low Levels

Zinc (Zn) and copper (Cu) are essential microelements, which take part in cellular metabolism, feature in enzymatic systems, and regulate enzyme activity. Homeostasis of these micronutrients is tightly regulated by multiple compensatory mechanisms that balance their concentrations including transporters, importers, and metallothioneins. An altered intake of only one of these trace elements may cause an imbalance in their levels and result in their competition for absorption. Relatively low levels of zinc and increased levels of copper may result in an increased level of oxidative stress and impair the antioxidant properties of multiple enzymes. Altered levels of trace elements were discovered in various pathologies including immunological, degenerative, and inflammatory diseases. Moreover, due to the role of Zn and Cu in oxidative stress and chronic inflammation, they were found to influence cancerogenesis. We review the roles of zinc and copper and their mechanisms in tumor growth, metastasis potential, microenvironment remodeling, and drug resistance. We highlight their role as potential biomarkers for cancer diagnosis, treatment, and prognosis, concentrating on their impact on gynecological malignancies.

scholarly journals RRM2B-Mediated Regulation of Mitochondrial Activity and Inflammation under Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Er-Chieh Cho ◽  
Mei-Ling Kuo ◽  
Jia-hui Cheng ◽  
Yu-Chi Cheng ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Signaling Pathway ◽  
Ribonucleotide Reductase ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Mitochondrial Activity ◽  
Independent Manner ◽  
Mitochondrial Homeostasis

RRM2B is a critical ribonucleotide reductase (RR) subunit that exists as p53-inducible and p53-dependent molecule. The p53-independent regulation of RRM2B has been recently studied, and FOXO3 was identified as a novel regulator of RRM2B. However, the p53-independent regulation of RRM2B, particularly under oxidative stress, remains largely unknown. In this study, we investigated the role of RRM2B underoxidative stress-induced DNA damage and further examined the regulation of mitochondrial and inflammatory genes by RRM2B. Our study is the first to report the critical role of RRM2B in mitochondrial homeostasis and the inflammation signaling pathway in a p53-independent manner. Furthermore, our study provides novel insights into the role of the RR in inflammatory diseases.

scholarly journals Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 743
Author(s):  
Da-Young Lee ◽  
Moon-Young Song ◽  
Eun-Hee Kim
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Transcription Factor ◽  
Cancer Progression ◽  
Inflammatory Diseases ◽  
Negative Regulator ◽  
Related Factor ◽  
Cancer Society ◽  
Incidence And Mortality

Colorectal cancer still has a high incidence and mortality rate, according to a report from the American Cancer Society. Colorectal cancer has a high prevalence in patients with inflammatory bowel disease. Oxidative stress, including reactive oxygen species (ROS) and lipid peroxidation, has been known to cause inflammatory diseases and malignant disorders. In particular, the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-related protein 1 (KEAP1) pathway is well known to protect cells from oxidative stress and inflammation. Nrf2 was first found in the homolog of the hematopoietic transcription factor p45 NF-E2, and the transcription factor Nrf2 is a member of the Cap ‘N’ Collar family. KEAP1 is well known as a negative regulator that rapidly degrades Nrf2 through the proteasome system. A range of evidence has shown that consumption of phytochemicals has a preventive or inhibitory effect on cancer progression or proliferation, depending on the stage of colorectal cancer. Therefore, the discovery of phytochemicals regulating the Nrf2/KEAP1 axis and verification of their efficacy have attracted scientific attention. In this review, we summarize the role of oxidative stress and the Nrf2/KEAP1 signaling pathway in colorectal cancer, and the possible utility of phytochemicals with respect to the regulation of the Nrf2/KEAP1 axis in colorectal cancer.

scholarly journals Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases

Diseases ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 30
Author(s):  
Virna Margarita Martín Giménez ◽  
Natalia de las Heras ◽  
León Ferder ◽  
Vicente Lahera ◽  
Russel J. Reiter ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Metabolic Disorders ◽  
Inflammatory Diseases ◽  
Therapeutic Agents ◽  
Cytokine Storm ◽  
Natural Substances ◽  
Inflammatory Status ◽  
Close Relationship

Exaggerated oxidative stress and hyper-inflammation are essential features of oxidative/inflammatory diseases. Simultaneously, both processes may be the cause or consequence of mitochondrial dysfunction, thus establishing a vicious cycle among these three factors. However, several natural substances, including melatonin and micronutrients, may prevent or attenuate mitochondrial damage and may preserve an optimal state of health by managing the general oxidative and inflammatory status. This review aims to describe the crucial role of mitochondria in the development and progression of multiple diseases as well as the close relationship among mitochondrial dysfunction, oxidative stress, and cytokine storm. Likewise, it attempts to summarize the main findings related to the powerful effects of melatonin and some micronutrients (vitamins and minerals), which may be useful (alone or in combination) as therapeutic agents in the treatment of several examples of oxidative/inflammatory pathologies, including sepsis, as well as cardiovascular, renal, neurodegenerative, and metabolic disorders.

scholarly journals Proresolving Lipid Mediators: Endogenous Modulators of Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Alessandro Leuti ◽  
Mauro Maccarrone ◽  
Valerio Chiurchiù
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Diseases ◽  
Antioxidant Systems ◽  
Molecular Events ◽  
Inflammatory Processes ◽  
Endogenous Antioxidant ◽  
Endogenous Modulators ◽  
Species Production ◽  
Endogenous Lipids

Specialized proresolving mediators (SPMs) are a novel class of endogenous lipids, derived byω-6 andω-3 essential polyunsaturated fatty acids such as arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) that trigger and orchestrate the resolution of inflammation, which is the series of cellular and molecular events that leads to spontaneous regression of inflammatory processes and restoring of tissue homeostasis. These lipids are emerging as highly effective therapeutic agents that exert their immunoregulatory activity by activating the proresolving pathway, as reported by a consistent bulk of evidences gathered in the last two decades since their discovery. The production of reactive oxygen (ROS) and nitrogen (RNS) species by immune cells plays indeed an important role in the inflammatory mechanisms of host defence, and it is now clear that oxidative stress, viewed as an imbalance between such species and their elimination, can lead to many chronic inflammatory diseases. This review, the first of its kind, is aimed at exploring the manifold effects of SPMs on modulation of reactive species production, along with the mechanisms through which they either inhibit molecular signalling pathways that are activated by oxidative stress or induce the expression of endogenous antioxidant systems. Furthermore, the possible role of SPMs in oxidative stress-mediated chronic disorders is also summarized, suggesting not only that their anti-inflammatory and proresolving properties are strictly associated with their antioxidant role but also that these endogenous lipids might be exploited in the treatment of several pathologies in which uncontrolled production of ROS and RNS or impairment of the antioxidant machinery represents a main pathogenetic mechanism.

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