scholarly journals The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins

2017 ◽  
Vol 63 (4) ◽  
pp. 316-320
Author(s):  
O.A. Buneeva ◽  
A.T. Kopylov ◽  
L.N. Nerobkova ◽  
I.G. Kapitsa ◽  
V.G. Zgoda ◽  
...  

Isatin (indole-2,3-dione) is an endogenous indole found in the mammalian brain, peripheral organs and body fluids. It acts as a neuroprotector, which decreases manifestation of locomotor impairments in animal models of Parkinson's disease. A wide range of biological activity of isatin is associated with interaction of this regulator with numerous isatin-binding proteins. The aim of this study was to investigate the profile of brain isatin-binding proteins in mice with MPTP-induced Parkinsonism (90 min and seven days after administration of this neurotoxin). A single dose administration of MPTP (30 mg/kg, ip.) was accompanied by locomotor impairments in the open field test 90 min after administration; seven days after MPTP administration locomotor activity of mice significantly improved but did not reach the control level. Five independent experiments on proteomic profiling of isatin-binding proteins resulted in confident identification of 96±12 proteins. Development of MPTP-induced locomotor impairments was accompanied by a significant decrease in the number of isatin-binding proteins (63±6; n=5; p<0.01). Seven days after MPTP administration the total number of identified proteins increased and reached the control level (132±34; n=4). The profiles of isatin-binding proteins were rather specific for each group of mice: in the control group these proteins (which were not found in both groups of MPTP-treated mice) represented more than 70% of total proteins. In the case of MPTP treated mice this parameter was 60% (90 min after MPTP administration) and >82% (seven days after MPTP administration). The major changes were found in the groups of isatin-binding proteins involved into cytoskeleton formation and exocytosis, regulation of gene expression, cell division and differentiation and also proteins involved in signal transduction.

2019 ◽  
Vol 65 (5) ◽  
pp. 407-417 ◽  
Author(s):  
O.A. Buneeva ◽  
I.G. Kapitsa ◽  
E.A. Ivanova ◽  
A.T. Kopylov ◽  
V.G. Zgoda ◽  
...  

Isatin (indol-2,3-dione), an endogenous biofactor found in the brain, peripheral tissues and biological body fluids of humans and animals, exhibits a wide range of biological and pharmacological activities. They are realized via interaction with numerous isatin-binding proteins. Some of these proteins identified during proteomic profiling of the brain are involved in the development of neurodegenerative pathology. In the context of the neuroprotective effect, the effect of isatin is comparable to the effects of deprenyl (selegiline), a pharmacological agent used for treatment of Parkinson's disease. In this study, we have investigated the effect of a single dose administration of isatin (100 mg/kg) and deprenyl (10 mg/kg) to mice on the profile of the brain isatin-binding proteins. Comparative proteomic analysis of brain isatin-binding proteins of mice treated with isatin or deprenyl resulted in identification of a representative group of proteins (n=200) sensitive to the administration of these substances. The change in the profile of isatin-binding proteins may be obviously attributed to accumulation of isatin and deprenyl in the brain and their interaction with target proteins; this prevents protein binding to the affinity sorbent. Thus identified brain isatin-binding proteins of the control animals obviously represent specific targets that interact directly with isatin (and also with deprenyl) in vivo. Isatin or deprenyl administered to animals interact with these proteins and thus inhibit their binding to the affinity sorbent (immobilized isatin analogue).


2020 ◽  
Vol 27 (10) ◽  
pp. 971-978
Author(s):  
Hao Shen ◽  
Xiaosha Zhang ◽  
Md. Abdullah Al Hafiz ◽  
Xiaoting Liang ◽  
Qiting Yao ◽  
...  

Background: Prmt5 plays major role in regulation of gene expression, RNA processing, cell growth and differentiation, signal transduction, germ cell development, etc., in mammals. Prmt5 is also related to cancer. Knowing the proteins interacting with Prmt5 is important to understand Prmt5’s function in cells. Although there have been reports on proteins binding with Prmt5 in mammals, the partner proteins of Prmt5 in fish are still unclear. Objectives: The objective was to obtain proteins that bind with Prmt5 in medaka, a model fish. Methods: Yeast two hybridization was adopted to achieve the objective. Medaka Prmt5 was used as a bait to fish the prey, binding proteins in a cDNA library of medaka. Co-immunoprecipitation and in silicon analysis were performed to study the interaction of medaka Mep50 and Prmt5. Results: Eight proteins were identified to bind with Prmt5 from 69 preliminary positive colonies. The binding proteins are methylosome protein 50 (Mep50), apolipoprotein A-I-like (Apo-AI), PR domain containing protein 1a with zinc fingers (Prdm1a), Prdm1b, T-cell immunoglobulin mucin family member 3 (Tim-3), phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (Paics), NADH dehydrogenase subunit 4 (ND4) and sciellin (Scl). Co-immunoprecipitation confirmed the interaction of medaka Prmt5 and Mep50. Predicted structures of medaka Prtm5 and Mep50 are similar to that of human PRMT5 and MEP50. Conclusion: Medaka Mep50, Prdm1a, Prdm1b, Apo-AI, Tim-3, Paics, ND4, and Scl bind with Prmt5.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Isela Álvarez-González ◽  
Scarlett Camacho-Cantera ◽  
Patricia Gómez-González ◽  
Michael J. Rendón Barrón ◽  
José A. Morales-González ◽  
...  

AbstractWe evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.


Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 122
Author(s):  
Marta Pérez-Rodríguez ◽  
Saleky García-Gómez ◽  
Javier Coterón ◽  
Juan José García-Hernández ◽  
Javier Pérez-Tejero

Background and objectives: Acquired brain injury (ABI) is the first cause of disability and physical activity (PA) is a key element in functional recovery and health-related quality of life (HRQoL) during the subacute and chronic phases. However, it is necessary to develop PA programs that respond to the heterogeneity and needs of this population. The aim of this study was to assess the effectiveness of a PA program on the HRQoL in this population. Materials and Methods: With regard to recruitment, after baseline evaluations, participants were assigned to either the intervention group (IG, n = 38) or the control group (CG, n = 35). Functional capacity, mood, quality of life and depression were measured pre- and post-intervention. The IG underwent the “Physical Activity and Sport for Acquired Brain Injury” (PASABI) program, which was designed to improve HRQoL (1-h sessions, two to four sessions/week for 18 weeks). The CG underwent a standard rehabilitation program without PA. Results: Results for the IG indicated significant differences and large effect sizes for the physical and mental dimensions of quality of life, as well as mood and functional capacity, indicating an increase in HRQoL. No significant differences were found for the CG across any variables. Conclusions: The PASABI program was feasible and beneficial for improving physiological and functionality variables in the IG. The wide range of the activities of the PASABI program allow its application to a large number of people with ABI, promoting health through PA, especially in the chronic phase.


Author(s):  
Magdalena Mijas ◽  
Karolina Koziara ◽  
Andrzej Galbarczyk ◽  
Grazyna Jasienska

A risk of cardiovascular disease (CVD) is increased by multiple factors including psychosocial stress and health behaviors. Sexual minority men who identify as Bears form a subculture distinguished by characteristics associated with increased CVD risk such as elevated stress and high body weight. However, none of the previous studies comprehensively investigated CVD risk in this population. Our study compared Bears (N = 31) with other gay men (N = 105) across a wide range of CVD risk factors. Logistic regression and analysis of covariance (ANCOVA) models were performed to compare both groups concerning behavioral (e.g., physical activity), medical (e.g., self-reported hypertension), and psychosocial (e.g., depressiveness) CVD risk factors. Bears were characterized by older age and higher body mass index (BMI) than the control group. We also observed higher resilience, self-esteem, as well as greater prevalence of self-reported hypertension, diabetes, and hypercholesterolemia in Bears. None of these differences remained statistically significant after adjusting for age and, in the case of self-reported diagnosis of diabetes, both age and BMI. Our study demonstrates that Bears are characterized by increased CVD risk associated predominantly with older age and higher BMI. Health promotion interventions addressed to this community should be tailored to Bears’ subcultural norms and should encourage a healthier lifestyle instead of weight loss.


Coatings ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Reham Z. Hamza ◽  
Mohammad S. Al-Harbi ◽  
Munirah A. Al-Hazaa

Aging is a neurological disease that is afforded by incidence of oxidative stress. Chitosan has received global interests due to its wide medical uses. Quercetin (Q) is a bioflavonoid and widely distributed in vegetables and fruits. Resveratrol is considered as a potent antioxidant and is a component of a wide range of foods. The using of either chitosan nanopartciles (CH-NPs), querectin (Q), and resveratrol (RV) to reduce the oxidative stress and biochemical alterations on brain and testicular tissues induced by D-galactose (DG) (100 mg/Kg) were the aim of the present study. This study investigated the probable protective effects of CH-NPs in two doses (140,280 mg/Kg), Q (20 mg/Kg) and RV (20 mg/Kg), against DG induced aging and neurological alterations. Brain antioxidant capacity as malonaldehyde (MDA), catalase (CAT), and glutathione reductase (GRx), as well as histopathological damages of the brain and testicular tissues were measured. The DG treated group had significantly elevated the oxidative stress markers by 96% and 91.4% in brain and testicular tissues respectively and lower significantly the antioxidant enzyme activities of both brain and testicular tissues than those of the control group by 86.95%, 69.27%, 83.07%, and 69.43%. Groups of DG that treated with a combination of CH-NPs in two doses, Q and RV, the levels of oxidative stress marker declined significantly by 68.70%, 76.64% in brain tissues and by 74.07% and 76.61% in testicular tissues, and the enzymatic antioxidants increased significantly by 75.55%, 79.24%, 62.32%, and 61.97% as compared to the DG group. The present results indicate that CH-NPs, Q, and RV have protective effects against DG-induced brain and testis tissue damage at the biochemical and histopathological levels. Mechanisms of this protective effect of used compounds against neurological and testicular toxicity may be due to the enhanced brain and testis antioxidant capacities.


2021 ◽  
pp. 338607
Author(s):  
Yunming Liu ◽  
Minghui Qu ◽  
Mengting Pan ◽  
Xiaofang Zheng ◽  
Yuwei Sheng ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2693
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro

The development and maturation of the mammalian brain are regulated by thyroid hormones (THs). Both hypothyroidism and hyperthyroidism cause serious anomalies in the organization and function of the nervous system. Most importantly, brain development is sensitive to TH supply well before the onset of the fetal thyroid function, and thus depends on the trans-placental transfer of maternal THs during pregnancy. Although the mechanism of action of THs mainly involves direct regulation of gene expression (genomic effects), mediated by nuclear receptors (THRs), it is now clear that THs can elicit cell responses also by binding to plasma membrane sites (non-genomic effects). Genomic and non-genomic effects of THs cooperate in modeling chromatin organization and function, thus controlling proliferation, maturation, and metabolism of the nervous system. However, the complex interplay of THs with their targets has also been suggested to impact cancer proliferation as well as metastatic processes. Herein, after discussing the general mechanisms of action of THs and their physiological effects on the nervous system, we will summarize a collection of data showing that thyroid hormone levels might influence cancer proliferation and invasion.


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Shimaa Ibrahim Amin ◽  
Ghada Mohamed Salah EL-Deen

Abstract Background Autism is not a discreet condition and those families members with autistic propend are more likely to display autistic symptoms with a wide range of severity, even below the threshold for diagnosis of autism spectrum disorders. Even with a parental history of schizophrenia, the likelihood of autistic spectrum disorder was found to be 3-fold greater. The aim of this study is to assess autistic traits among offspring of schizophrenic patients in the age group from 4 to 11 years and compare it in the offspring of normal individuals, and its association with the sociodemographic data. To determine whether schizophrenic parents are a risk factor to autistic traits in their children. Results There was a statistically significant (P < 0.05*) increase in Autism Quotient Child scores of the case group where 47.2% had a score equal or more than the cutoff point (76), while only 17 19.4% of the control group had the same score with odds = 3.71 indicating that children of schizophrenic parents 18 were three times likely to have Autism Quotient-Child score greater than or equal to the cutoff point (76) than 19 children of healthy parents. No statistically significant association (P ≥ 0.05) was found between all 20 sociodemographic characteristics and Autism Quotient-Child scores among the case group except for family 21 income and social class where there was a statistically significant association (P < 0.05) between insufficient income 22 and low social class and higher Autism Quotient-Child score (≥ 76). Conclusions Children of schizophrenic parents are at high risk to have autistic traits than children of normal parents.


1986 ◽  
Vol 43 (2) ◽  
pp. 285-292 ◽  
Author(s):  
S. M. Rhind ◽  
B. A. Morris ◽  
Jill Clayton ◽  
J. M. Doney ◽  
R. G. Gunn ◽  
...  

ABSTRACTBorder Leicester × Scottish Blackface (Greyface) ewes of three groups, each comprising 118 animals in a wide range of body condition scores, were mated at a synchronized oestrus in mid October. The ewes were passively immunized against testosterone (group P), actively immunized against androstenedione (group F), or not treated (group C). All ewes were slaughtered at return to service or at 35 to 45 days of pregnancy and ovulation rates and numbers of embryos present were determined. Mean ovulation rates of ewes in group P were higher than in those in group C (P < 0·05) and this difference was evident at most levels of body condition. The absolute increase in ovulation rate, compared with the control group, was similar at all condition scores. Mean ovulation rates of ewes in group F were higher than those in group C (P < 0·001) and the magnitude of the increase was greater in ewes in higher condition scores. The incidence of ova wastage was variable but differences between treatments in mean ovulation rate were generally reflected in mean litter size. The conception rates of immunized ewes were depressed compared with those of control animals, particularly in ewes with a body condition score less than 3·0 at mating. Consequently, there was no improvement in the potential lambing rate of immunized ewes following only one cycle of mating. Circulating antibody titres were not related to conception rate or body condition at mating and were related to ovulation rate only in group F ewes. It is concluded that immunization against steroids, using either passive or active techniques, can improve the reproductive performance of individual ewes but improvement in the performance of the flock as a whole may only be achieved under optimal conditions of nutrition and season.


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