2’-Deoxyribose Mediated Glycation Leads to Alterations in BSA Structure Via Generation of Carbonyl Species

2020 ◽  
Vol 21 (9) ◽  
pp. 924-935
Author(s):  
Zeeshan Rafi ◽  
Sultan Alouffi ◽  
Mohd Sajid Khan ◽  
Saheem Ahmad
Keyword(s):  
Serum Protein ◽  
Band Shift ◽  
Reactive Carbonyl Species ◽  
Age Related ◽  
Model Protein ◽  
Living Organisms ◽  
Α Helix ◽  
Enzymatic Glycosylation ◽  
Carbonyl Species

The non-enzymatic glycosylation is a very common phenomenon in the physiological conditions which is mediated by distinct chemical entities containing reactive carbonyl species (RCS) and participates in the modification of various macromolecules particularly proteins. To date, various carbonyl species, i.e., glucose, fructose, D-ribose and methylglyoxal have been used frequently to assess the in-vitro non-enzymatic glycosylation. Similarly, 2'-Deoxyribose is one of the most abundant reducing sugar of the living organisms which forms the part of deoxyribonucleic acid and may react with proteins leading to the production of glycation intermediates, advanced glycation end products (AGEs) and highly reactive RCS. Thymidine phosphorylase derived degradation of thymidine contributes to the formation of 2'-Deoxyribose, therefore, acting as a major source of cellular 2'- Deoxyribose. Since albumin is a major serum protein which plays various roles including binding and transporting endogenous and exogenous ligands, it is more prone to be modified through different physiological modifiers; therefore, it may serve as a model protein for in-vitro experiments to study the effect of 2’Deoxyribose mediated modifications in the protein. In this study, Bovine Serum Albumin (BSA) was glycated with 50 and 100 mM 2'-Deoxyribose followed by examining secondary and tertiary structural modifications in BSA as compared to its native (unmodified) form by using various physicochemical techniques. We evident a significant modification in 2'-Deoxyribose-glycated BSA which was confirmed through increased hyperchromicity, keto amine moieties, carbonyl and hydroxymethylfurfural content, fluorescent AGEs, altered secondary structure conformers (α helix and β sheets), band shift in the amide-I region and diminished free lysine and free arginine content. These modifications were reported to be higher in 100 mM 2'-Deoxyribose-glycated BSA than 50 mM 2'- Deoxyribose-glycated BSA. Our findings also demonstrated that the rate of glycation is positively affected by the increased concentration of 2'-Deoxyribose. The results of the performed study can be implied to uncover the phenomenon of serum protein damage caused by 2'-Deoxyribose leading towards diabetic complications and the number of AGE-related diseases.

scholarly journals Treating Senescence like Cancer: Novel Perspectives in Senotherapy of Chronic Diseases

2020 ◽  
Vol 21 (21) ◽  
pp. 7984
Author(s):  
Alessia Mongelli ◽  
Sandra Atlante ◽  
Veronica Barbi ◽  
Tiziana Bachetti ◽  
Fabio Martelli ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Cell Senescence ◽  
Biological Processes ◽  
Social Relevance ◽  
Chemical Agents ◽  
Age Related ◽  
Living Organisms ◽  
Specific Pathway

The WHO estimated around 41 million deaths worldwide each year for age-related non-communicable chronic diseases. Hence, developing strategies to control the accumulation of cell senescence in living organisms and the overall aging process is an urgently needed problem of social relevance. During aging, many biological processes are altered, which globally induce the dysfunction of the whole organism. Cell senescence is one of the causes of this modification. Nowadays, several drugs approved for anticancer therapy have been repurposed to treat senescence, and others are under scrutiny in vitro and in vivo to establish their senomorphic or senolytic properties. In some cases, this research led to a significant increase in cell survival or to a prolonged lifespan in animal models, at least. Senomorphics can act to interfere with a specific pathway in order to restore the appropriate cellular function, preserve viability, and to prolong the lifespan. On the other hand, senolytics induce apoptosis in senescent cells allowing the remaining non–senescent population to preserve or restore tissue function. A large number of research articles and reviews recently addressed this topic. Herein, we would like to focus attention on those chemical agents with senomorphic or senolytic properties that perspectively, according to literature, suggest a potential application as senotherapeutics for chronic diseases.

The Disposal of Reactive Carbonyl Species through Carnosine Conjugation: What We Know Now

2020 ◽  
Vol 27 (11) ◽  
pp. 1726-1743 ◽  
Author(s):  
Ettore Gilardoni ◽  
Giovanna Baron ◽  
Alessandra Altomare ◽  
Marina Carini ◽  
Giancarlo Aldini ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Current Knowledge ◽  
Therapeutic Agents ◽  
New Drugs ◽  
Reactive Carbonyl Species ◽  
Carbonyl Species ◽  
Reactive Carbonyl

: Reactive Carbonyl Species are electrophiles generated by the oxidative cleavage of lipids and sugars. Such compounds have been described as important molecules for cellular signaling, whilst their accumulation has been found to be cytotoxic as they may trigger aberrant modifications of proteins (a process often referred to as carbonylation). : A correlation between carbonylation of proteins and human disease progression has been shown in ageing, diabetes, obesity, chronic renal failure, neurodegeneration and cardiovascular disease. However, the fate of reactive carbonyl species is still far from being understood, especially concerning the mechanisms responsible for their disposal as well as the importance of this in disease progression. : In this context, some data have been published on phase I and phase II deactivation of reactive carbonyl species. In the case of phase II mechanisms, the route involving glutathione conjugation and subsequent disposal of the adducts has been extensively studied both in vitro and in vivo for some of the more representative compounds, e.g. 4-hydroxynonenal. : There is also emerging evidence of an involvement of carnosine as an endogenous alternative to glutathione for phase II conjugation. However, the fate of carnosine conjugates is still poorly investigated and, unlike glutathione, there is little evidence of the formation of carnosine adducts in vivo. The acquisition of such data could be of importance for the development of new drugs, since carnosine and its derivatives have been proposed as potential therapeutic agents for the mitigation of carbonylation associated with disease progression. : Herein, we wish to review our current knowledge of the binding of reactive carbonyl species with carnosine together with the disposal of carnosine conjugates, emphasizing those aspects still requiring investigation such as conjugation reversibility and enzyme assisted catalysis of the reactions.

scholarly journals Immunosenescence in some but not all immune components in a free-living vertebrate, the tree swallow

2007 ◽  
Vol 274 (1612) ◽  
pp. 951-957 ◽  
Author(s):  
Maria G Palacios ◽  
Joan E Cunnick ◽  
David W Winkler ◽  
Carol M Vleck
Keyword(s):  
T Cell ◽  
Immune Function ◽  
Tree Swallow ◽  
Future Research ◽  
Cell Mediated Immunity ◽  
Free Living ◽  
Age Related ◽  
Living Organisms

A wide diversity of free-living organisms show increases in mortality rates and/or decreases in reproductive success with advancing age. However, the physiological mechanisms underlying these demographic patterns of senescence are poorly understood. Immunosenescence, the age-related deterioration of immune function, is well documented in humans and laboratory models, and often leads to increased morbidity and mortality due to disease. However, we know very little about immunosenescence in free-living organisms. Here, we studied immunosenescence in a free-living population of tree swallows, Tachycineta bicolor , assessing three components of the immune system and using both in vivo and in vitro immunological tests. Immune function in tree swallow females showed a complex pattern with age; acquired T-cell mediated immunity declined with age, but neither acquired nor innate humoral immunity did. In vitro lymphocyte proliferation stimulated by T-cell mitogens decreased with age, suggesting that reduced T-cell function might be one mechanism underlying the immunosenescence pattern of in vivo cell-mediated response recently described for this same population. Our results provide the most thorough description of immunosenescence patterns and mechanisms in a free-living vertebrate population to date. Future research should focus on the ecological implications of immunosenescence and the potential causes of variation in patterns among species.

A novel multi-target strategy to attenuate the progression of Parkinson's disease by diamine hybrid AGE/ALE inhibitor

2021 ◽  
Author(s):  
N André Sasaki ◽  
Pascal Sonnet
Keyword(s):  
Reactive Oxygen Species ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Reactive Carbonyl Species ◽  
Vacuum Cleaning ◽  
Carbonyl Species ◽  
Reactive Carbonyl

Instead of a conventional ‘one-drug-one-target approach’, this article presents a novel multi-target approach with a concept of trapping simultaneously as many detrimental factors as possible involved in the progression of Parkinson's disease. These factors include reactive carbonyl species, reactive oxygen species, Fe3+/Cu2+ and ortho-quinones ( o-quinone), in particular. Different from the known multi-target strategies for Parkinson's disease, it is a sort of ‘vacuum cleaning’ strategy. The new agent consists of reactive carbonyl species scavenging moiety and reactive oxygen species scavenging and metal chelating moiety linked by a spacer. Provided that the capacity of scavenging o-quinones is demonstrated, this type of agent can further broaden its potential therapeutic profile. In order to support this new hypothetical approach, a number of simple in vitro experiments are proposed.

Age-Related Changes in the Effects of Serum from Lean and Obese Pigs on Myogenic Cell Proliferation in Vitro

1982 ◽  
Vol 54 (4) ◽  
pp. 763-768 ◽  
Author(s):  
Ronald E. Allen ◽  
Gail Robinson ◽  
Matthew J. Parsons ◽  
Robert A. Merkel ◽  
William T. Magee
Keyword(s):  
Cell Proliferation ◽  
Myogenic Cell ◽  
Age Related ◽  
Proliferation In Vitro ◽  
Age Related Changes

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim
Keyword(s):  
New Host ◽  
In Vivo Models ◽  
Vector Borne Diseases ◽  
Novel Drugs ◽  
Huge Impact ◽  
Tick Borne Disease ◽  
Vector Borne ◽  
Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

A Pro-Somathropic Formulation with GHR Agonistic and Pro-Thyrogenic Features (Preprint)

2019 ◽  
Author(s):  
Erdal Can Alkoclar
Keyword(s):  
Mrna Expression ◽  
Efficient Method ◽  
Age Related

BACKGROUND A Formulation consisting of 2 Dioscin and 2 Glucopyranoside Derivatives with Simultaneous GHRH Stimulative and T3 mRNA Expression Enhancimg Features. OBJECTIVE Anti Aging METHODS GH/T3 Optimization RESULTS Approved in Vitro CONCLUSIONS Endogenous GH and T3 Optimization is the an efficient method for combating age related Senility and Fatigue Symptoms

Renal Cortical Slices: An In Vitro Model for Kidney Metabolism and Toxicity

1992 ◽  
Vol 20 (1) ◽  
pp. 71-76
Author(s):  
Andrea Trevisan ◽  
Stefano Maso ◽  
Paola Meneghetti
Keyword(s):  
Wistar Rats ◽  
Reduced Glutathione ◽  
Organic Anion ◽  
Cortical Slice ◽  
Lactate Dehydrogenase Release ◽  
Age Related ◽  
Renal Cortical Slice ◽  
Male Wistar Rats ◽  
Vitro Model

The in vitro renal cortical slice model was used to study: 1) the effects on the kidney of some haloalkanes and haloalkenes using 3-month-old male Wistar rats; 2) influence of age and sex on renal cortical slice indices in non-treated rats; and 3) effects of 1,2-dichloropropane on the slices after pretreatment of 3-month-old male Wistar rats with DL-butathionine-[S,R]-sulphoximine. The most nephrotoxic chemical used was 1,3-dichloropropene, which caused a total depletion in the levels of reduced glutathione, a high peroxidation of lipid (about three thousand-fold with respect to control), a significant release of tubular enzymes into the medium, and loss of organic anion ( p-aminohippurate) accumulation. All the chemicals affected the cytosol more than the brush border. The most remarkable age-related differences in the untreated slices were the progressive decrease of reduced glutathione (p<0.05 from three months of age), and an increase in lactate dehydrogenase release into the medium (p<0.05 from six months of age). By contrast, sex differences were slight. The ‘treatment with 1,2-dichloropropane of slices prepared from rats pretreated with DL-butathionine-[S,R]-sulphoximine significantly increased the depletion of glutathione content (p<0.05) and malondialdehyde release in the medium (p<0.001) caused by the solvent alone.

scholarly journals Analgesic and Anti-Inflammatory Effects of Aucklandia lappa Root Extracts on Acetic Acid-Induced Writhing in Mice and Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Plants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Hee-Geun Jo ◽  
Geon-Yeong Lee ◽  
Chae Yun Baek ◽  
Ho Sueb Song ◽  
Donghun Lee
Keyword(s):  
Acetic Acid ◽  
Weight Bearing ◽  
Bone Diseases ◽  
Joint Disease ◽  
Root Extracts ◽  
Raw264.7 Macrophages ◽  
Age Related ◽  
Monosodium Iodoacetate ◽  
Anti Inflammatory

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions. We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1β, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1β, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA.

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