Species-specific effects on non-enzymatic metmyoglobin reduction in vitro

The effects of nitromethylene heterocycle (NMH) insecticides on subtypes of nicotinic acetylcholine (nACh) receptors were investigated in locust thoracic ganglion neurons, mouse N1E-115 neuroblastoma cells, and mouse BC3H1 muscle cells by using electrophysiological techniques. In locust neurons, all of the six NMH insecticides tested induced transient inward currents resembling nicotinic ACh-induced inward currents, while, in the continued presence of the NMH compounds, the ACh-induced inward current was blocked. The amplitude of the inward current and the blocking effects of the NMH insecticides were enhanced by concentrations between 0.1 and 10μM. Cross-desensitisation with the ACh-induced inward current confirmed that the NMH-induced inward current was governed by the activation of nACh receptors. Mammalian endplate type nACh receptors in BC3H1 cells and mammalian neuronal type nACh receptors in N1E-115 cells were much less sensitive to the NMH insecticides than the locust neuronal nACh receptors. At a concentration of 10μM, which blocked 80–100% of the ACh-induced inward current in locust neurons, NMH insecticides only partially blocked the ACh-induced inward currents mediated by the two subtypes of mammalian nACh receptors. NMH insecticides also failed to induce significant agonist effects in the mammalian cells at this concentration. The results provide a possible explanation for the selectively greater toxicity of NMH insecticides to insects than to vertebrates, at the level of nACh receptor subtypes and, hence, demonstrate that this in vitro approach is valuable for the investigation of species-specific interactions of compounds at their target site.

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Urea and KCl have differential effects on enzyme activities in liver and muscle of estivating versus nonestivating species

Biochemistry and Cell Biology ◽

10.1139/o02-144 ◽

2002 ◽

Vol 80 (6) ◽

pp. 745-755 ◽

Cited By ~ 14

Author(s):

Kyra J Cowan ◽

Kenneth B Storey

Keyword(s):

Polyethylene Glycol ◽

Enzyme Activities ◽

Leopard Frog ◽

Leopard Frogs ◽

Spadefoot Toads ◽

Specific Effects ◽

Total Body ◽

Species Specific ◽

Protein Crowding

The effects of 300 mM urea or 300 mM KCl on the maximal activities of 25 enzymes of intermediary metabolism were assessed in extracts of liver and muscle from spadefoot toads (Scaphiopus couchii), leopard frogs (Rana pipiens), and rats to assess their sensitivity to these osmolytes. During estivation, toads can lose ~50% of total body water, and urea, which is known for its action as a protein denaturant, accumulates to 200300 mM. The data show that the maximal activities of toad liver enzymes were not affected when assayed in the presence of 300 mM urea in vitro whereas urea inhibited the activities of seven enzymes in frog and 11 enzymes in rat liver. High KCl affected 12 or 13 enzymes in liver of each species causing inhibition in eight or nine cases each, and for frog and rat enzymes, inhibition was frequently more pronounced than for urea. Both urea and KCl affected enzyme activities in muscle extracts of all three species, but whereas their effects were largely negative for frog and rat enzymes, the enzymes affected by urea or KCl in toad muscle were primarily activated by these osmolytes (six out of nine enzymes affected by urea and eight of 15 enzymes affected by KCl). Urea, KCl, and polyethylene glycol (a protein crowding agent) also had species-specific effects on the dissociation constant (Ka) for cAMP of protein kinase A. The data suggest that the accumulation of urea by water-stressed anurans not only contributes to minimizing cell volume reduction, but by doing so also limits the increase in intracellular ionic strength that occurs and thereby helps to minimize the potential inhibitory effects of high salts on metabolic enzymes.Key words: estivation, desiccation, urea, polyethylene glycol, spadefoot toad, leopard frog.

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Invited Review: Cross-bridge regulation by thin filament-associated proteins

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.2.953 ◽

2001 ◽

Vol 91 (2) ◽

pp. 953-962 ◽

Cited By ~ 174

Author(s):

Kathleen G. Morgan ◽

Samudra S. Gangopadhyay

Keyword(s):

Thin Filament ◽

Smooth Muscle Actin ◽

Actin Binding ◽

Specific Effects ◽

Associated Proteins ◽

Considerable Controversy ◽

Species Specific ◽

Available Information

This minireview will cover current concepts on the identity and mechanistic function of smooth muscle actin binding proteins that may regulate actin-myosin interactions. The potential roles of tropomyosin, caldesmon, calponin, and SM22 will be discussed. The review, for purposes of brevity, will be nonexhaustive but will give an overview of available information on the in vitro biochemistry and potential in vivo function of these proteins. Preterm labor is discussed as a possible example of where thin filament regulation may be relevant. Considerable controversy surrounds the putative physiological significance of these proteins, and emphasis will be placed on the need for more experimental work to determine the degree to which tissue- and species-specific effects have clouded the interpretation of functional data.

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Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205017666200317092310 ◽

2020 ◽

Vol 17 (2) ◽

pp. 141-157 ◽

Cited By ~ 2

Author(s):

Dubravka S. Strac ◽

Marcela Konjevod ◽

Matea N. Perkovic ◽

Lucija Tudor ◽

Gordana N. Erjavec ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Large Scale ◽

Therapeutic Potential ◽

Relevant Literature ◽

Comprehensive Overview ◽

Brain Functions ◽

Specific Effects ◽

And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

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Novel Toxin-antitoxin System Xn-mazEF from Xenorhabdus nematophi-la: Identification, Characterization and Functional Exploration

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200625135850 ◽

2020 ◽

Vol 16 ◽

Author(s):

Jogendra Singh Nim ◽

Mohit Yadav ◽

Lalit Kumar Gautam ◽

Chaitali Ghosh ◽

Shakti Sahi ◽

...

Keyword(s):

Interaction Analysis ◽

Functional Characterization ◽

Host Cells ◽

System Control ◽

Xenorhabdus Nematophila ◽

Functional Features ◽

Dynamics Simulations ◽

Species Specific ◽

Rna Interaction

Background: Xenorhabdus nematophila maintains species-specific mutual interaction with nematodes of Steinernema genus. Type II Toxin Antitoxin (TA) systems, the mazEF TA system controls stress and programmed cell death in bacteria. Objective: This study elucidates the functional characterization of Xn-mazEF, a mazEF homolog in X. nematophila by computational and in vitro approaches. Methods: 3 D- structural models for Xn-MazE toxin and Xn-MazF antitoxin were generated, validated and characterized for protein - RNA interaction analysis. Further biological and cellular functions of Xn-MazF toxin were also predicted. Molecular dynamics simulations of 50ns for Xn-MazF toxin complexed with nucleic acid units (DU, RU, RC, and RU) were performed. The MazF toxin and complete MazEF operon were endogenously expressed and monitored for the killing of Escherichia coli host cells under arabinose induced tightly regulated system. Results: Upon induction, E. coli expressing toxin showed rapid killing within four hours and attained up to 65% growth inhibition, while the expression of the entire operon did not show significant killing. The observation suggests that the Xn-mazEF TA system control transcriptional regulation in X. nematophila and helps to manage stress or cause toxicity leading to programmed death of cells. Conclusion: The study provides insights into structural and functional features of novel toxin, XnMazF and provides an initial inference on control of X. nematophila growth regulated by TA systems.

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Total weak acid concentration and effective dissociation constant of nonvolatile buffers in human plasma

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.3.1364 ◽

2001 ◽

Vol 91 (3) ◽

pp. 1364-1371 ◽

Cited By ~ 31

Author(s):

Peter D. Constable

Keyword(s):

Dissociation Constant ◽

Human Plasma ◽

Total Concentration ◽

Weak Acid ◽

Strong Ion Difference ◽

Acid Base ◽

Horse Plasma ◽

Using Data ◽

Species Specific

The strong ion approach provides a quantitative physicochemical method for describing the mechanism for an acid-base disturbance. The approach requires species-specific values for the total concentration of plasma nonvolatile buffers (Atot) and the effective dissociation constant for plasma nonvolatile buffers ( K a), but these values have not been determined for human plasma. Accordingly, the purpose of this study was to calculate accurate Atot and K a values using data obtained from in vitro strong ion titration and CO2tonometry. The calculated values for Atot (24.1 mmol/l) and K a (1.05 × 10−7) were significantly ( P < 0.05) different from the experimentally determined values for horse plasma and differed from the empirically assumed values for human plasma (Atot = 19.0 meq/l and K a = 3.0 × 10−7). The derivatives of pH with respect to the three independent variables [strong ion difference (SID), Pco 2, and Atot] of the strong ion approach were calculated as follows: [Formula: see text] [Formula: see text], [Formula: see text]where S is solubility of CO2 in plasma. The derivatives provide a useful method for calculating the effect of independent changes in SID+, Pco 2, and Atot on plasma pH. The calculated values for Atot and K a should facilitate application of the strong ion approach to acid-base disturbances in humans.

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Pan-American Lancehead Pit-Vipers: Coagulotoxic Venom Effects and Antivenom Neutralisation of Bothrops asper and B. atrox Geographical Variants

Toxins ◽

10.3390/toxins13020078 ◽

2021 ◽

Vol 13 (2) ◽

pp. 78

Author(s):

Lachlan A. Bourke ◽

Christina N. Zdenek ◽

Edgar Neri-Castro ◽

Melisa Bénard-Valle ◽

Alejandro Alagón ◽

...

Keyword(s):

Evolutionary Biology ◽

Current Knowledge ◽

Clinical Manifestations ◽

In Vivo Studies ◽

Factor X ◽

Clotting Factors ◽

Bothrops Asper ◽

Species Specific

The toxin composition of snake venoms and, thus, their functional activity, can vary between and within species. Intraspecific venom variation across a species’ geographic range is a major concern for antivenom treatment of envenomations, particularly for countries like French Guiana that lack a locally produced antivenom. Bothrops asper and Bothrops atrox are the most medically significant species of snakes in Latin America, both producing a variety of clinical manifestations, including systemic bleeding. These pathophysiological actions are due to the activation by the venom of the blood clotting factors Factor X and prothrombin, thereby causing severe consumptive coagulopathy. Both species are extremely wide-ranging, and previous studies have shown their venoms to exhibit regional venom variation. In this study, we investigate the differential coagulotoxic effects on human plasma of six venoms (four B. asper and two B. atrox samples) from different geographic locations, spanning from Mexico to Peru. We assessed how the venom variation of these venom samples affects neutralisation by five regionally available antivenoms: Antivipmyn, Antivipmyn-Tri, PoliVal-ICP, Bothrofav, and Soro Antibotrópico (SAB). The results revealed both inter- and intraspecific variations in the clotting activity of the venoms. These variations in turn resulted in significant variation in antivenom efficacy against the coagulotoxic effects of these venoms. Due to variations in the venoms used in the antivenom production process, antivenoms differed in their species-specific or geographical neutralisation capacity. Some antivenoms (PoliVal-ICP, Bothrofav, and SAB) showed species-specific patterns of neutralisation, while another antivenom (Antivipmyn) showed geographic-specific patterns of neutralisation. This study adds to current knowledge of Bothrops venoms and also illustrates the importance of considering evolutionary biology when developing antivenoms. Therefore, these results have tangible, real-world implications by aiding evidence-based design of antivenoms for treatment of the envenomed patient. We stress that these in vitro studies must be backed by future in vivo studies and clinical trials before therapeutic guidelines are issued regarding specific antivenom use in a clinical setting.

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Combining species specific in vitro & in silico models to predict in vivo food effect in a preclinical stage – case study of Venetoclax

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2021.105840 ◽

2021 ◽

pp. 105840

Author(s):

Laura J. Henze ◽

Niklas J. Koehl ◽

Joseph P. O'Shea ◽

René Holm ◽

Maria Vertzoni ◽

...

Keyword(s):

In Silico ◽

Food Effect ◽

Preclinical Stage ◽

Species Specific ◽

In Silico Models

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Seminal Plasma: Relevant for Fertility?

International Journal of Molecular Sciences ◽

10.3390/ijms22094368 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4368

Author(s):

Heriberto Rodriguez-Martinez ◽

Emilio A. Martinez ◽

Juan J. Calvete ◽

Fernando J. Peña Vega ◽

Jordi Roca

Keyword(s):

Seminal Plasma ◽

Current Knowledge ◽

Inorganic Ions ◽

Vitro Fertilization ◽

Dna And Rna ◽

Model Animal ◽

Sexual Glands ◽

Species Specific

Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA—the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans.

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