scholarly journals Physiological Ovarian Aging Is Associated with Altered Expression of Post-Translational Modifications in Mice

2021 ◽  
Vol 23 (1) ◽  
pp. 2
Author(s):  
Minli Wei ◽  
Jia Li ◽  
Huili Yan ◽  
Tao Luo ◽  
Jiang Huang ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Quantitative Real Time Pcr ◽  
Altered Expression ◽  
Post Translational Modifications ◽  
Ovarian Aging ◽  
Regulatory Enzymes ◽  
Histone Lysine ◽  
Genes Encoding ◽  
Aging Models ◽  
Reproductive Events

Post-translational modifications (PTMs) have been confirmed to be involved in multiple female reproductive events, but their role in physiological ovarian aging is far from elucidated. In this study, mice aged 3, 12 or 17 months (3M, 12M, 17M) were selected as physiological ovarian aging models. The expression of female reproductive function-related genes, the global profiles of PTMs, and the level of histone modifications and related regulatory enzymes were examined during physiological ovarian aging in the mice by quantitative real-time PCR and western blot, respectively. The results showed that the global protein expression of Kbhb (lysineβ-hydroxybutyryllysine), Khib (lysine 2-hydroxyisobutyryllysine), Kglu (lysineglutaryllysine), Kmal (lysinemalonyllysine), Ksucc (lysinesuccinyllysine), Kcr (lysinecrotonyllysine), Kbu (lysinebutyryllysine), Kpr (lysinepropionyllysine), SUMO1 (SUMO1 modification), ub (ubiquitination), P-Typ (phosphorylation), and 3-nitro-Tyr (nitro-tyrosine) increased significantly as mice aged. Moreover, the modification level of Kme2 (lysinedi-methyllysine) and Kac (lysineacetyllysine) was the highest in the 3M mice and the lowest in 12M mice. In addition, only trimethylation of histone lysine was up-regulated progressively and significantly with increasing age (p < 0.001), H4 ubiquitination was obviously higher in the 12M and 17M mice than 3M (p < 0.001), whereas the modification of Kpr (lysinepropionylation) and O-GlcNA in 17M was significantly decreased compared with the level in 3M mice (p < 0.05, p < 0.01). Furthermore, the expression levels of the TIP60, P300, PRDM9, KMT5B, and KMT5C genes encoding PTM regulators were up-regulated in 17M compared to 3M female mice (p < 0.05). These findings indicate that altered related regulatory enzymes and PTMs are associated with physiological ovarian aging in mice, which is expected to provide useful insights for the delay of ovarian aging and the diagnosis and treatment of female infertility.

scholarly journals Macromolecule biosynthesis: a key function of sleep

2007 ◽  
Vol 31 (3) ◽  
pp. 441-457 ◽  
Author(s):  
Miroslaw Mackiewicz ◽  
Keith R. Shockley ◽  
Micah A. Romer ◽  
Raymond J. Galante ◽  
John E. Zimmerman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Sleep Deprivation ◽  
Expression Patterns ◽  
State Level ◽  
Altered Expression ◽  
Mouse Cerebral Cortex ◽  
Genes Encoding ◽  
Function Of Sleep ◽  
Cellular Components

The function(s) of sleep remains a major unanswered question in biology. We assessed changes in gene expression in the mouse cerebral cortex and hypothalamus following different durations of sleep and periods of sleep deprivation. There were significant differences in gene expression between behavioral states; we identified 3,988 genes in the cerebral cortex and 823 genes in the hypothalamus with altered expression patterns between sleep and sleep deprivation. Changes in the steady-state level of transcripts for various genes are remarkably common during sleep, as 2,090 genes in the cerebral cortex and 409 genes in the hypothalamus were defined as sleep specific and changed (increased or decreased) their expression during sleep. The largest categories of overrepresented genes increasing expression with sleep were those involved in biosynthesis and transport. In both the cerebral cortex and hypothalamus, during sleep there was upregulation of multiple genes encoding various enzymes involved in cholesterol synthesis, as well as proteins for lipid transport. There was also upregulation during sleep of genes involved in synthesis of proteins, heme, and maintenance of vesicle pools, as well as antioxidant enzymes and genes encoding proteins of energy-regulating pathways. We postulate that during sleep there is a rebuilding of multiple key cellular components in preparation for subsequent wakefulness.

scholarly journals The association of C789A polymorphism in the dopamine beta-hydroxylase gene (DBH) and aggressive behaviour in dogs

2021 ◽  
Vol 90 (3) ◽  
pp. 295-299
Author(s):  
Daniel Polasik ◽  
Aneta Konieczna ◽  
Arkadiusz Terman ◽  
Andrzej Dybus
Keyword(s):  
Aggressive Behaviour ◽  
Pcr Amplification ◽  
Polymerase Chain Reaction Method ◽  
Emotional States ◽  
Signalling Molecules ◽  
Regulatory Enzymes ◽  
Dopamine Beta Hydroxylase ◽  
Hydroxylase Gene ◽  
Behavioural Characteristics ◽  
Genes Encoding

The genetic basis of aggressive behaviour has been examined extensively, including analysis of genes encoding neurotransmitters, signalling molecules and regulatory enzymes, as well as their synthesis and degradation. Dopamine beta-hydroxylase, an enzyme catalysing the conversion of dopamine into norepinephrine in synaptic endings, significantly affects the modulation of emotional states and behaviour. The aim of this study was to determine the association of C789A polymorphism in the canine dopamine beta-hydroxylase gene (DBH) and aggressive behaviour in dogs. A total of 110 dogs of different breeds were analysed. All animals were classified according to their individual behavioural characteristics, defined by a veterinary interview and observation. Polymorphism was analysed using ACRS-PCR (amplification created restriction site-polymerase chain reaction) method. Significant differences in DBH genotypes and allele frequency between aggressive and non-aggressive dogs were observed (χ2 = 16,232, P = 0.0003). In aggressive dogs, the CC genotype (0.788) and C allele (0.815) were most frequent while in non-aggressive dogs, their frequencies were significantly lower (0.361 and 0.404, respectively). The obtained results indicate that DBH is a promising candidate gene for canine behavioural study.

scholarly journals Age-dependent changes in electrophysiology and calcium handling – implications for pediatric cardiac research

2019 ◽  
Author(s):  
Luther M. Swift ◽  
Morgan Burke ◽  
Devon Guerrelli ◽  
Manelle Ramadan ◽  
Marissa Reilly ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Cardiac Electrophysiology ◽  
Calcium Handling ◽  
Cell Coupling ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Age Dependent ◽  
Genes Encoding ◽  
Cardiac Maturation

ABSTRACTRationaleThe heart continues to develop and mature after birth and into adolescence. Accordingly, cardiac maturation is likely to include a progressive refinement in both organ morphology and function during the postnatal period. Yet, age-dependent changes in cardiac electrophysiology and calcium handling have not yet been fully characterized.ObjectiveThe objective of this study, was to examine the relationship between cardiac maturation, electrophysiology, and calcium handling throughout postnatal development in a rat model.MethodsPostnatal rat cardiac maturation was determined by measuring the expression of genes involved in cell-cell coupling, electrophysiology, and calcium handling. In vivo electrocardiograms were recorded from neonatal, juvenile, and adult animals. Simultaneous dual optical mapping of transmembrane voltage and calcium transients was performed on isolated, Langendorff-perfused rat hearts (postnatal day 0–3, 4-7, 8-14, adult).ResultsYounger, immature hearts displayed slowed electrical conduction, prolonged action potential duration and increased ventricular refractoriness. Slowed calcium handling in the immature heart increased the propensity for calcium transient alternans which corresponded to alterations in the expression of genes encoding calcium handling proteins. Developmental changes in cardiac electrophysiology were associated with the altered expression of genes encoding potassium channels and intercalated disc proteins.ConclusionUsing an intact whole heart model, this study highlights chronological changes in cardiac electrophysiology and calcium handling throughout postnatal development. Results of this study can serve as a comprehensive baseline for future studies focused on pediatric cardiac research, safety assessment and/or preclinical testing using rodent models.

scholarly journals Minimization of energy transduction confers resistance to phosphine in the rice weevil, Sitophilus oryzae

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kyeongnam Kim ◽  
Jeong Oh Yang ◽  
Jae-Yoon Sung ◽  
Ji-Young Lee ◽  
Jeong Sun Park ◽  
...  
Keyword(s):  
Cancer Metabolism ◽  
Insect Pests ◽  
Sitophilus Oryzae ◽  
Resistance Mechanism ◽  
Energy Transduction ◽  
Metabolic Reprogramming ◽  
Rice Weevil ◽  
Altered Expression ◽  
Synonymous Mutations ◽  
Genes Encoding

Abstract Infestation of phosphine (PH3) resistant insects threatens global grain reserves. PH3 fumigation controls rice weevil (Sitophilus oryzae) but not highly resistant insect pests. Here, we investigated naturally occurring strains of S. oryzae that were moderately resistant (MR), strongly resistant (SR), or susceptible (wild-type; WT) to PH3 using global proteome analysis and mitochondrial DNA sequencing. Both PH3 resistant (PH3–R) strains exhibited higher susceptibility to ethyl formate-mediated inhibition of cytochrome c oxidase than the WT strain, whereas the disinfectant PH3 concentration time of the SR strain was much longer than that of the MR strain. Unlike the MR strain, which showed altered expression levels of genes encoding metabolic enzymes involved in catabolic pathways that minimize metabolic burden, the SR strain showed changes in the mitochondrial respiratory chain. Our results suggest that the acquisition of strong PH3 resistance necessitates the avoidance of oxidative phosphorylation through the accumulation of a few non-synonymous mutations in mitochondrial genes encoding complex I subunits as well as nuclear genes encoding dihydrolipoamide dehydrogenase, concomitant with metabolic reprogramming, a recognized hallmark of cancer metabolism. Taken together, our data suggest that reprogrammed metabolism represents a survival strategy of SR insect pests for the compensation of minimized energy transduction under anoxic conditions. Therefore, understanding the resistance mechanism of PH3–R strains will support the development of new strategies to control insect pests.

scholarly journals Ablation of sarcolipin results in atrial remodeling

2012 ◽  
Vol 302 (12) ◽  
pp. C1762-C1771 ◽  
Author(s):  
Lai-Hua Xie ◽  
Mayilvahanan Shanmugam ◽  
Ji Yeon Park ◽  
Zhenghang Zhao ◽  
Hairuo Wen ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Calcium Transient ◽  
Atrial Remodeling ◽  
Atrial Myocytes ◽  
Long Term Effects ◽  
Sodium Calcium Exchanger ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Intracellular Ca

Sarcolipin (SLN) is a key regulator of sarco(endo)plasmic reticulum (SR) Ca2+-ATPase (SERCA), and its expression is altered in diseased atrial myocardium. To determine the precise role of SLN in atrial Ca2+ homeostasis, we developed a SLN knockout ( sln−/−) mouse model and demonstrated that ablation of SLN enhances atrial SERCA pump activity. The present study is designed to determine the long-term effects of enhanced SERCA activity on atrial remodeling in the sln−/− mice. Calcium transient measurements show an increase in atrial SR Ca2+ load and twitch Ca2+ transients. Patch-clamping experiments demonstrate activation of the forward mode of sodium/calcium exchanger, increased L-type Ca2+ channel activity, and prolongation of action potential duration at 90% repolarization in the atrial myocytes of sln−/− mice. Spontaneous Ca2+ waves, delayed afterdepolarization, and triggered activities are frequent in the atrial myocytes of sln−/− mice. Furthermore, loss of SLN in atria is associated with increased interstitial fibrosis and altered expression of genes encoding collagen and other extracellular matrix proteins. Our results also show that the sln−/− mice are susceptible to atrial arrhythmias upon aging. Together, these findings indicate that ablation of SLN results in increased SERCA activity and SR Ca2+ load, which, in turn, could cause abnormal intracellular Ca2+ handling and atrial remodeling.

scholarly journals Structural insight into HEMK2–TRMT112-mediated glutamine methylation

2020 ◽  
Vol 477 (19) ◽  
pp. 3833-3838
Author(s):  
Jie Gao ◽  
Bin Wang ◽  
Huijuan Yu ◽  
Gao Wu ◽  
Cuihong Wan ◽  
...  
Keyword(s):  
Release Factor ◽  
Lysine Methylation ◽  
Catalytic Complex ◽  
Post Translational Modifications ◽  
Histone Lysine Methylation ◽  
Cellular Events ◽  
Histone Lysine ◽  
Protein Functions ◽  
Insight Into

Post-translational modifications play important roles in mediating protein functions in a wide variety of cellular events in vivo. HEMK2–TRMT112 heterodimer has been reported to be responsible for both histone lysine methylation and eukaryotic release factor 1 (eRF1) glutamine methylation. However, how HEMK2–TRMT112 complex recognizes and catalyzes eRF1 glutamine methylation is largely unknown. Here, we present two structures of HEMK2–TRMT112, with one bound to SAM and the other bound with SAH and methylglutamine (Qme). Structural analyses of the post-catalytic complex, complemented by mass spectrometry experiments, indicate that the HEMK2 utilizes a specific pocket to accommodate the substrate glutamine and catalyzes the subsequent methylation. Therefore, our work not only throws light on the protein glutamine methylation mechanism, but also reveals the dual activity of HEMK2 by catalyzing the methylation of both Lys and Gln residues.

scholarly journals Nα-terminal acetylation of proteins by NatA and NatB serves distinct physiological roles in Saccharomyces cerevisiae

2019 ◽  
Author(s):  
Ulrike A. Friedrich ◽  
Mostafa Zedan ◽  
Bernd Hessling ◽  
Kai Fenzl ◽  
Ludovic Gillet ◽  
...  
Keyword(s):  
Stress Responses ◽  
Ribosomal Proteins ◽  
Protein Modification ◽  
Protein Quality ◽  
Biological Significance ◽  
General Role ◽  
Altered Expression ◽  
Phenotypic Differences ◽  
Genes Encoding

SummaryN-terminal (Nt)-acetylation is a highly prevalent co-translational protein modification in eukaryotes, catalyzed by at least five Nt-acetyltransferases (Nat) with differing specificities. Nt-acetylation has been implicated in protein quality control but its broad biological significance remains elusive. We investigated the roles of the two major Nats of S. cerevisiae, NatA and NatB, by performing transcriptome, translatome and proteome profiling of natAΔ and natBΔ mutants. Our results do not support a general role of Nt-acetylation in protein degradation but reveal an unexpected range of Nat-specific phenotypes. NatA is implicated in systemic adaptation control, as natAΔ mutants display altered expression of transposons, sub-telomeric genes, pheromone response genes and nuclear genes encoding mitochondrial ribosomal proteins. NatB predominantly affects protein folding, as natBΔ mutants accumulate protein aggregates, induce stress responses and display reduced fitness in absence of the ribosome-associated chaperone Ssb. These phenotypic differences indicate that controlling Nat activities may serve to elicit distinct cellular responses.

scholarly journals Reduced Expression of Slc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience

2020 ◽  
Author(s):  
Dmitry A. Smagin ◽  
Vladimir N. Babenko ◽  
Irina L. Kovalenko ◽  
Anna G. Galyamina ◽  
Olga E. Redina ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Differentially Expressed ◽  
Male Mice ◽  
Agonistic Interactions ◽  
Specific Expression ◽  
Chronic Stimulation ◽  
Altered Expression ◽  
Slc Transporters ◽  
Genes Encoding ◽  
Complete Disruption

ABSTRACTThere are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of the Slc* genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressed Slc genes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressed Slc genes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose, etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of the Slc* genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems.

scholarly journals Combinatory Treatment with miR-7-5p and Drug-Loaded Cubosomes Effectively Impairs Cancer Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 5039
Author(s):  
Ewa Gajda ◽  
Marlena Godlewska ◽  
Zenon Mariak ◽  
Ewa Nazaruk ◽  
Damian Gawel
Keyword(s):  
Cancer Cells ◽  
Free Drug ◽  
Drug Resistant ◽  
Papillary Thyroid ◽  
Quantitative Real Time Pcr ◽  
Promising Strategy ◽  
Novel Approach ◽  
Genes Encoding ◽  
Test Flow ◽  
Induction Of Apoptosis

Background: Multidrug resistance (MDR) is an emerging problem in the treatment of cancer. Therefore, there is a necessity for novel strategies that would sensitize tumor cells to the administered chemotherapeutics. One of the innovative approaches in fighting drug-resistant tumors is the treatment of cancer with microRNA (miRNA), or the use of cubosomes (lipid nanoparticles) loaded with drugs. Here, we present a study on a novel approach, which combines both tools. Methods: Cubosomes loaded with miR-7-5p and chemotherapeutics were developed. The effects of drug- and miRNA-loaded vehicles on glioma- (A172, T98G), papillary thyroid- (TPC-1) and cervical carcinoma-derived (HeLa) cells were analyzed using molecular biology techniques, including quantitative real-time PCR, MTS-based cell proliferation test, flow cytometry and spheroids formation assay. Results: The obtained data indicate that miR-7-5p increases the sensitivity of the tested cells to the drug, and that nanoparticles loaded with both miRNA and the drug produce a greater anti-tumor effect in comparison to the free drug treatment. It was found that an increased level of apoptosis in the drug/miRNA co-treated cells is accompanied by an alternation in the expression of the genes encoding for key MDR proteins of the ABC family. Conclusions: Overall, co-administration of miR-7-5p with a chemotherapeutic can be considered a promising strategy, leading to reduced MDR and the induction of apoptosis in cancer cells.

scholarly journals Relation between Biofilm and Virulence in Vibrio tapetis: A Transcriptomic Study

Pathogens ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 92 ◽  
Author(s):  
Sophie Rodrigues ◽  
Christine Paillard ◽  
Sabine Van Dillen ◽  
Ali Tahrioui ◽  
Jean-Marc Berjeaud ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Cell System ◽  
Ruditapes Philippinarum ◽  
Differentially Expressed ◽  
Type Vi Secretion System ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Polysaccharide Synthesis ◽  
Genes Encoding ◽  
Genetic Level

Marine pathogenic bacteria are able to form biofilms on many surfaces, such as mollusc shells, and they can wait for the appropriate opportunity to induce their virulence. Vibrio tapetis can develop such biofilms on the inner surface of shells of the Ruditapes philippinarum clam, leading to the formation of a brown conchiolin deposit in the form of a ring, hence the name of the disease: Brown Ring Disease. The virulence of V. tapetis is presumed to be related to its capacity to form biofilms, but the link has never been clearly established at the physiological or genetic level. In the present study, we used RNA-seq analysis to identify biofilm- and virulence-related genes displaying altered expression in biofilms compared to the planktonic condition. A flow cell system was employed to grow biofilms to obtain both structural and transcriptomic views of the biofilms. We found that 3615 genes were differentially expressed, confirming that biofilm and planktonic lifestyles are very different. As expected, the differentially expressed genes included those involved in biofilm formation, such as motility- and polysaccharide synthesis-related genes. The data show that quorum sensing is probably mediated by the AI-2/LuxO system in V. tapetis biofilms. The expression of genes encoding the Type VI Secretion System and associated exported proteins are strongly induced, suggesting that V. tapetis activates this virulence factor when living in biofilm.

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