Regulating the level of intracellular hydrogen peroxide: the role of peroxiredoxin IV

2014 ◽  
Vol 42 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Rachel E. Martin ◽  
Zhenbo Cao ◽  
Neil J. Bulleid

Hydrogen peroxide (H2O2) can act as a signalling molecule affecting the cell cycle as well as contributing towards the oxidative stress response. The primary target of this molecule is oxidation-sensitive cysteine residues in proteins such as protein tyrosine phosphatases. The cell has robust mechanisms to remove H2O2 that need to be regulated for H2O2 to react with and modify protein thiols. In particular, the family of peroxiredoxins are capable of the rapid removal of even trace amounts of this molecule. It has been suggested that the inactivation of peroxiredoxins by hyperoxidation may allow H2O2 levels to increase in cells and thereby modify critical thiol groups in proteins. We have been studying how the H2O2 produced during disulfide formation in the ER (endoplasmic reticulum) is metabolized and have shown that ER-resident peroxiredoxin IV not only can remove H2O2, but also contributes to de novo disulfide formation. In the present article, we review recent data on the structure and function of this enzyme as well as its sensitivity to hyperoxidation.

Author(s):  
Diana Hamdan ◽  
Lisa A. Robinson

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.


2020 ◽  
Author(s):  
Qian Dong ◽  
Michael Zavortink ◽  
Francesca Froldi ◽  
Sofya Golenkina ◽  
Tammy Lam ◽  
...  

AbstractThe final size and function of the adult central nervous system (CNS) is determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation, and non-autonomously restrained to prevent ectopic Hh signalling in the NBs. In the context of cortex glial overgrowth, induced by Fibroblast Growth Factor (FGF) activation, Hh and lipid storage regulators Lsd-2 and Fasn1 were upregulated, resulting in activation of Hh signalling in the NBs; which in turn disrupted NB cell cycle progression and reduced neuronal production. We show that the LD regulator Lsd-2 modulates Hh’s ability to signal to NBs, and de novo lipogenesis gene Fasn1 regulates Hh post-translational modification via palmitoylation. Together, our data suggest that the glial niche non-autonomously regulates NB proliferation and neural lineage size via Hh signaling that is modulated by lipid metabolism genes.


Development ◽  
1997 ◽  
Vol 124 (5) ◽  
pp. 1007-1018 ◽  
Author(s):  
J.F. Celis de

The differentiation of the veins in the Drosophila wing involves the coordinate activities of several signal transduction pathways, including those mediated by the transmembrane receptors Torpedo and Notch. In this report, the role of the signalling molecule Decapentaplegic during vein differentiation has been analysed. It is shown that decapentaplegic is expressed in the pupal veins under the control of genes that establish vein territories in the imaginal disc. Decapentaplegic, acting through its receptor Thick veins, activates vein differentiation and restricts expression of both veinlet and the Notch-ligand Delta to the developing veins. Genetic combinations between mutations that increase or reduce Notch, veinlet and decapentaplegic activities suggest that the maintenance of the vein differentiation state during pupal development involves cross-regulatory interactions between these pathways.


2019 ◽  
Vol 9 (2) ◽  
pp. 359
Author(s):  
Misnawati Misnawati ◽  
Hasbi ◽  
Abd Rasyid J ◽  
Yusriadi Yusriadi ◽  
Saidna Zulfiqar Bin-Tahir

The Family Hope Program (PKH) is one of government policy programs in poverty alleviation by involving the main actor who called PPKH. This study aimed to describe the task and function of PPKH in empowering the sick society in Bone Regency. Qualitative approach used with case study research. Data collection techniques used was interviews, observation, and documentation. The instrument in this study was the researcher himself as a human instrument, while the informants selected by a purposive method. Data analysis techniques used an interactive model includes data collection, data reduction, data presentation, verification, and conclusion. The results of the study showed that PPKH has carried out their roles well as representatives and technicians but have not been optimal in their roles as facilitators and educators.


2017 ◽  
Vol 3 (1) ◽  
pp. 61
Author(s):  
Hasan Basri

Madrasah in the Middle East has known eight or nine centuries before madrasah in Indonesia, which emerged as a reaction to the reform movement as well as a response to the policy of Dutch colonizers secular education. Madrasah got a decent place in Indonesia after rising SKB 3 minister (Minister of Interior, Minister of Education and Culture, and the Minister of Religious Affairs) in 1975, where madrasas equated with other schools in terms of the status of the diploma, graduates continuing education opportunities and changing schools. In a further development, the school as disoriented. It is caused by two things: first, a paradigm shift towards sekularistik. Education implementation has marred even be interpreted as a partial instead of a holistic paradigm as desired by Islam. Supposedly, the madrasa education as a whole should make Islam as a principle in the determination of educational objectives, the formulation of the curriculum and standard of value of science and the learning process, including determining the qualifications of teachers and school culture that will be developed in the madrasas. Second, the functional institutional weakness as a result of shifting the orientation and function of the family and their influence and societal demands materialistic-hedonistic.The weakness seen in a mess madrasa curriculum, not optimal role of teachers as well as school culture that is not in line with the will of Islam.


2021 ◽  
pp. mcs.a006122
Author(s):  
Mohammad Marhabaie ◽  
Scott E Hickey ◽  
Katherine E Miller ◽  
Olivia Grischow ◽  
Kathleen M Schieffer ◽  
...  

There is increasing recognition for the contribution of genetic mosaicism to human disease, particularly as high-throughput sequencing has enabled detection of sequence variants at very low allele frequencies. Here, we describe an infant male who presented at 9 months of age with hypotonia, dysmorphic features, congenital heart disease, hyperinsulinemic hypoglycemia, hypothyroidism, and bilateral sensorineural hearing loss. Whole-genome sequencing of the proband and the parents uncovered an apparent de novo mutation in the X-linked SMS gene. SMS encodes spermine synthase, which catalyzes the production of spermine from spermidine. Inactivation of the SMS gene disrupts the spermidine/spermine ratio, resulting in Snyder-Robinson syndrome. The variant in our patient is absent from the gnomAD and ExAC databases and causes a missense change (p.Arg130Cys) predicted to be damaging by most in silico tools. While Sanger sequencing confirmed the de novo status in our proband, PCR and deep targeted resequencing to ~84,000-175,000x depth revealed that the variant is present in blood from the unaffected mother at ~3% variant allele frequency. Our findings thus provided a long-sought diagnosis for the family while highlighting the role of parental mosaicism in severe genetic disorders.


2020 ◽  
Vol 3 (1) ◽  
pp. 3
Author(s):  
Nadya Tamara Dewaanjani ◽  
Sudarsana Sudarsana

<p>Family is one of the social institutions in the community. Family is also a place for children to acquire mental coaching and personality formation. The family has a considerable role and function on the development and future of the child. However, in fact the violence of children in the family often occurs, such as violence involving fathers, mothers and other siblings. Lack of knowledge and insight related to parenting, growth and development of children is one factor in the occurrence of violence against children. From various cases of child violence, one of NGO named Yayasan SAMIN that cares about child issues to make efforts to prevent and treat child violence in the family. This research aims to know 1) how the role of Yayasan SAMIN in the prevention and handling of child violence in the family, 2) How to form the prevention and handling conducted by the Yayasan SAMIN against Child abuse cases in Family. The results of this study show that 1) Yayasan SAMIN has been explaining its role in the prevention of child violence against parents and the treatment of child abuse victims in families, 2) The prevention of child violence by parents is socialization, campaigning, and KIE (communication, information, education). The form of treatment of victims of violence is with mentoring.</p>


2021 ◽  
Vol 3 (2) ◽  
pp. 1-9
Author(s):  
Heppi Sasmita, Neviyarni S, Yarmis Syukur

Every family wants harmony in the family. Awareness of the role and function of accepting circumstances and existence is a very strong foundation in running a household. In realizing a harmonious household, of course there are problems that must be resolved immediately so that family harmony is maintained and realized. The family has an important role in the success of the child, remembering that most of the time in the child's daily life with the family, the family is the first community for the child to interact. But in this digital era, many people of all ages have really changed. Changing to be fast paced, but also decreasing the harmony that has been established in the family, this can be seen by the reduced love, cooperation and sharing in the family because they are busy with their respective activities, especially when dealing with gadgets so that harmony in the family is reduced. The role of school counselors is indispensable in forming empathy for family members to achieve household harmony by using family counseling, which is used as an intervention process for problems that interfere with family harmony. Family counseling seeks to build closer bonds, individuals who are able to control emotions, and families who always have good communication in realizing family harmony.


Author(s):  
Marina Campione ◽  
Amelia Aranega ◽  
Diego Franco

Dextral looping is a complex process which progresses concomitantly with cardiac chamber differentiation and ultimately leads to the final alignment of the cardiac regions. Generation of cardiac asymmetry is crucial to ensure the proper form and consequent function of the heart and thus is a highly regulated process. Molecular signals originate long before morphological asymmetry and therefore can direct it; a complex regulatory network has been characterized which invariably converges on the Tgf-β‎ signalling molecule Nodal and its downstream target, the homeobox transcription factor Pitx2. We review current data regarding the cellular and molecular bases of cardiac looping and laterality, and describe current understaning of the role of Nodal and Pitx2. The morphogenetic role of the Pitx2 gene and its modulation of transcription and function, which have recently linked laterality to atrial fibrillation, are emphasized.


2020 ◽  
Vol 71 (9) ◽  
pp. 2782-2795 ◽  
Author(s):  
Shea M Monihan ◽  
Courtney A Magness ◽  
Choong-Hwan Ryu ◽  
Michelle M McMahon ◽  
Mark A Beilstein ◽  
...  

Abstract The presence of varied numbers of CALCINEURIN B-LIKE10 (CBL10) calcium sensor genes in species across the Brassicaceae and the demonstrated role of CBL10 in salt tolerance in Arabidopsis thaliana and Eutrema salsugineum provided a unique opportunity to determine if CBL10 function is modified in different species and linked to salt tolerance. Salinity effects on species growth and cross-species complementation were used to determine the extent of conservation and divergence of CBL10 function in four species representing major lineages within the core Brassicaceae (A. thaliana, E. salsugineum, Schrenkiella parvula, and Sisymbrium irio) as well as the first diverging lineage (Aethionema arabicum). Evolutionary and functional analyses indicate that CBL10 duplicated within expanded lineage II of the Brassicaceae and that, while portions of CBL10 function are conserved across the family, there are species-specific variations in CBL10 function. Paralogous CBL10 genes within a species diverged in expression and function probably contributing to the maintenance of the duplicated gene pairs. Orthologous CBL10 genes diverged in function in a species-specific manner, suggesting that functions arose post-speciation. Multiple CBL10 genes and their functional divergence may have expanded calcium-mediated signaling responses and contributed to the ability of certain members of the Brassicaceae to maintain growth in salt-affected soils.


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