scholarly journals The Multifaceted Role of HSF1 in Pathophysiology: Focus on Its Interplay with TG2

2021 ◽  
Vol 22 (12) ◽  
pp. 6366
Author(s):  
Luca Occhigrossi ◽  
Manuela D’Eletto ◽  
Nickolai Barlev ◽  
Federica Rossin
Keyword(s):  
Heat Shock ◽  
Metabolic Diseases ◽  
Cell Function ◽  
Main Role ◽  
Protein Homeostasis ◽  
Pathological Conditions ◽  
Cellular Environment ◽  
Role Concerns ◽  
Main Regulator

The cellular environment needs to be strongly regulated and the maintenance of protein homeostasis is crucial for cell function and survival. HSF1 is the main regulator of the heat shock response (HSR), the master pathway required to maintain proteostasis, as involved in the expression of the heat shock proteins (HSPs). HSF1 plays numerous physiological functions; however, the main role concerns the modulation of HSPs synthesis in response to stress. Alterations in HSF1 function impact protein homeostasis and are strongly linked to diseases, such as neurodegenerative disorders, metabolic diseases, and different types of cancers. In this context, type 2 Transglutaminase (TG2), a ubiquitous enzyme activated during stress condition has been shown to promote HSF1 activation. HSF1-TG2 axis regulates the HSR and its function is evolutionary conserved and implicated in pathological conditions. In this review, we discuss the role of HSF1 in the maintenance of proteostasis with regard to the HSF1-TG2 axis and we dissect the stress response pathways implicated in physiological and pathological conditions.

scholarly journals Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 104
Author(s):  
Elisa Fernández-Millán ◽  
Carlos Guillén
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Cell Biology ◽  
Pancreatic Beta Cells ◽  
Metabolic Diseases ◽  
Cell Function ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Short Chain Fatty Acids

Type 2 diabetes (T2D) results from impaired beta-cell function and insufficient beta-cell mass compensation in the setting of insulin resistance. Current therapeutic strategies focus their efforts on promoting the maintenance of functional beta-cell mass to ensure appropriate glycemic control. Thus, understanding how beta-cells communicate with metabolic and non-metabolic tissues provides a novel area for investigation and implicates the importance of inter-organ communication in the pathology of metabolic diseases such as T2D. In this review, we provide an overview of secreted factors from diverse organs and tissues that have been shown to impact beta-cell biology. Specifically, we discuss experimental and clinical evidence in support for a role of gut to beta-cell crosstalk, paying particular attention to bacteria-derived factors including short-chain fatty acids, lipopolysaccharide, and factors contained within extracellular vesicles that influence the function and/or the survival of beta cells under normal or diabetogenic conditions.

scholarly journals When the chains do not break: the role of USP10 in physiology and pathology

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Udayan Bhattacharya ◽  
Fiifi Neizer-Ashun ◽  
Priyabrata Mukherjee ◽  
Resham Bhattacharya
Keyword(s):  
Complex Formation ◽  
Molecular Mechanisms ◽  
Protein Homeostasis ◽  
Post Translational Modification ◽  
Intracellular Protein ◽  
Lysosomal Degradation ◽  
Life Activity ◽  
Cellular Processes ◽  
Pathological Conditions

AbstractDeubiquitination is now understood to be as important as its partner ubiquitination for the maintenance of protein half-life, activity, and localization under both normal and pathological conditions. The enzymes that remove ubiquitin from target proteins are called deubiquitinases (DUBs) and they regulate a plethora of cellular processes. DUBs are essential enzymes that maintain intracellular protein homeostasis by recycling ubiquitin. Ubiquitination is a post-translational modification where ubiquitin molecules are added to proteins thus influencing activation, localization, and complex formation. Ubiquitin also acts as a tag for protein degradation, especially by proteasomal or lysosomal degradation systems. With ~100 members, DUBs are a large enzyme family; the ubiquitin-specific peptidases (USPs) being the largest group. USP10, an important member of this family, has enormous significance in diverse cellular processes and many human diseases. In this review, we discuss recent studies that define the roles of USP10 in maintaining cellular function, its involvement in human pathologies, and the molecular mechanisms underlying its association with cancer and neurodegenerative diseases. We also discuss efforts to modulate USPs as therapy in these diseases.

scholarly journals Altered Ca2+ Homeostasis in Immune Cells during Aging: Role of Ion Channels

2020 ◽  
Vol 22 (1) ◽  
pp. 110
Author(s):  
Dorina Zöphel ◽  
Chantal Hof ◽  
Annette Lis
Keyword(s):  
Immune Cells ◽  
Irreversible Process ◽  
Cell Function ◽  
Immune Cell ◽  
Compensatory Mechanisms ◽  
Cellular Environment ◽  
Age Related ◽  
Dependent Processes ◽  
Equal Density

Aging is an unstoppable process and begins shortly after birth. Each cell of the organism is affected by the irreversible process, not only with equal density but also at varying ages and with different speed. Therefore, aging can also be understood as an adaptation to a continually changing cellular environment. One of these very prominent changes in age affects Ca2+ signaling. Especially immune cells highly rely on Ca2+-dependent processes and a strictly regulated Ca2+ homeostasis. The intricate patterns of impaired immune cell function may represent a deficit or compensatory mechanisms. Besides, altered immune function through Ca2+ signaling can profoundly affect the development of age-related disease. This review attempts to summarize changes in Ca2+ signaling due to channels and receptors in T cells and beyond in the context of aging.

scholarly journals Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Twan J. J. de Winter ◽  
Roeland Nusse
Keyword(s):  
Wnt Signaling ◽  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Cell Mass ◽  
Terminal Differentiation ◽  
Precursor Cell ◽  
Main Role ◽  
Histone Modifying Enzymes ◽  
Wnt Inhibitors

Mesenchymal stem cells (MSCs) give rise to adipocytes, osteocytes, and chondrocytes and reside in various tissues, including bone marrow and adipose tissue. The differentiation choices of MSCs are controlled by several signaling pathways, including the Wnt/β-catenin signaling. When MSCs undergo adipogenesis, they first differentiate into preadipocytes, a proliferative adipocyte precursor cell, after which they undergo terminal differentiation into mature adipocytes. These two steps are controlled by the Wnt/β-catenin pathway, in such a way that when signaling is abrogated, the next step in adipocyte differentiation can start. This sequence suggests that the main role of Wnt/β-catenin signaling is to suppress differentiation while increasing MSC and preadipocytes cell mass. During later steps of MSC differentiation, however, active Wnt signaling can promote osteogenesis instead of keeping the MSCs undifferentiated and proliferative. The exact mechanisms behind the various functions of Wnt signaling remain elusive, although recent research has revealed that during lineage commitment of MSCs into preadipocytes, Wnt signaling is inactivated by endogenous Wnt inhibitors. In part, this process is regulated by histone-modifying enzymes, which can lead to increased or decreased Wnt gene expression. The role of Wnt in adipogenesis, as well as in osteogenesis, has implications for metabolic diseases since Wnt signaling may serve as a therapeutic target.

Heat Shock Factor (HSF): The Promoter of Chaperone Genes. A Mini Review

2018 ◽  
Vol 16 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Natália Galdi Quel ◽  
Carlos H.I. Ramos
Keyword(s):  
Heat Shock ◽  
Molecular Chaperones ◽  
Protein Quality ◽  
Cell Function ◽  
Heat Shock Factor ◽  
Protein Homeostasis ◽  
General Knowledge ◽  
Protein Quality Control System ◽  
Shock Proteins ◽  
And Function

Protein homeostasis, or proteostasis, is required for proper cell function and thus must be under tight maintenance in all circumstances. In crowded cell conditions, protein folding is sometimes unfavorable, and this condition is worsened during stress situations. Cells cope with such stress through the use of a Protein Quality Control system, which uses molecular chaperones and heat shock proteins as its major players. This system aids with folding, avoiding misfolding and/or reversing aggregation. A pivotal regulator of the response to heat stress is Heat Shock Factor, which is recruited to the promoters of the chaperone genes, inducting their expression. This mini review aims to cover our general knowledge on the structure and function of this factor.

scholarly journals HSP Transcript and Protein Accumulation in Brassinosteroid Barley Mutants Acclimated to Low and High Temperatures

2020 ◽  
Vol 21 (5) ◽  
pp. 1889 ◽  
Author(s):  
Iwona Sadura ◽  
Marta Libik-Konieczny ◽  
Barbara Jurczyk ◽  
Damian Gruszka ◽  
Anna Janeczko
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Hormonal Regulation ◽  
Protein Accumulation ◽  
Main Role ◽  
Wild Type ◽  
Temperature Dependent ◽  
Shock Proteins

In temperature stress, the main role of heat-shock proteins (HSP) is to act as molecular chaperones for other cellular proteins. However, knowledge about the hormonal regulation of the production of the HSP is quite limited. Specifically, little is known about the role of the plant steroid hormones—brassinosteroids (BR)—in regulating the HSP expression. The aim of our study was to answer the question of how a BR deficit or disturbances in its signaling affect the accumulation of the HSP90, HSP70, HSP18, and HSP17 transcripts and protein in barley growing at 20 °C (control) and during the acclimation of plants at 5 °C and 27 °C. In barley, the temperature of plant growth modified the expression of HSPs. Furthermore, the BR-deficient mutants (mutations in the HvDWARF or HvCPD genes) and BR-signaling mutants (mutation in the HvBRI1 gene) were characterized by altered levels of the transcripts and proteins of the HSP group compared to the wild type. The BR-signaling mutant was characterized by a decreased level of the HSP transcripts and heat-shock proteins. In the BR-deficient mutants, there were temperature-dependent cases when the decreased accumulation of the HSP70 and HSP90 transcripts was connected to an increased accumulation of these HSP. The significance of changes in the accumulation of HSPs during acclimation at 27 °C and 5 °C is discussed in the context of the altered tolerance to more extreme temperatures of the studied mutants (i.e., heat stress and frost, respectively).

scholarly journals Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Qihang Hou ◽  
Yuanyang Dong ◽  
Jingxi Huang ◽  
Chaoyong Liao ◽  
Jiaqi Lei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stromal Cells ◽  
Cell Function ◽  
Mammalian Target Of Rapamycin ◽  
Cell Activity ◽  
Adult Stem Cell ◽  
Pathological Conditions ◽  
Stem Cell Activity ◽  
Small Intestinal

Abstract The renewal and repair of intestinal epithelium depend on the self-renewal of intestinal stem cells (ISCs) under physiological and pathological conditions. Although previous work has established that exogenous nutrients regulate adult stem cell activity, little is known about the regulatory effect of L-arginine on ISCs. In this study we utilize mice and small intestinal (SI) organoid models to clarify the role of L-arginine on epithelial differentiation of ISCs. We show that L-arginine increases expansion of ISCs in mice. Furthermore, CD90+ intestinal stromal cells augment stem-cell function in response to L-arginine in co-culture experiments. Mechanistically, we find that L-arginine stimulates Wnt2b secretion by CD90+ stromal cells through the mammalian target of rapamycin complex 1 (mTORC1) and that blocking Wnt2b production prevents L-arginine-induced ISC expansion. Finally, we show that L-arginine treatment protects the gut in response to injury. Our findings highlight an important role for CD90+ stromal cells in L-arginine-stimulated ISC expansion.

Chaperone-Mediated Protein Folding

1999 ◽  
Vol 79 (2) ◽  
pp. 425-449 ◽  
Author(s):  
Anthony L. Fink
Keyword(s):  
Protein Folding ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Chaperones ◽  
Main Role ◽  
Detailed Understanding ◽  
Substrate Protein ◽  
Reaction Cycles ◽  
Polypeptide Chains

The folding of most newly synthesized proteins in the cell requires the interaction of a variety of protein cofactors known as molecular chaperones. These molecules recognize and bind to nascent polypeptide chains and partially folded intermediates of proteins, preventing their aggregation and misfolding. There are several families of chaperones; those most involved in protein folding are the 40-kDa heat shock protein (HSP40; DnaJ), 60-kDa heat shock protein (HSP60; GroEL), and 70-kDa heat shock protein (HSP70; DnaK) families. The availability of high-resolution structures has facilitated a more detailed understanding of the complex chaperone machinery and mechanisms, including the ATP-dependent reaction cycles of the GroEL and HSP70 chaperones. For both of these chaperones, the binding of ATP triggers a critical conformational change leading to release of the bound substrate protein. Whereas the main role of the HSP70/HSP40 chaperone system is to minimize aggregation of newly synthesized proteins, the HSP60 chaperones also facilitate the actual folding process by providing a secluded environment for individual folding molecules and may also promote the unfolding and refolding of misfolded intermediates.

scholarly journals The History of the Discovery of Parathyroid Glands, and Their Role in the Body

2019 ◽  
Vol 74 (1) ◽  
pp. 35-43
Author(s):  
Natalia G. Mokrysheva ◽  
Julia A. Krupinova
Keyword(s):  
Modern Medicine ◽  
The Body ◽  
Parathyroid Glands ◽  
Main Role ◽  
Phosphorus Metabolism ◽  
Pathological Conditions ◽  
Long Time ◽  
Calcium Phosphorus ◽  
History Of

Currently, the parathyroid glands (PG) are admited as vital organs in humans. At the same time, the way to this acknowledgment was long and difficult, and the establishment of a link between the pathological conditions of the PG and their complications passed through many mistakes and errors. Understanding the regulation of calcium-phosphorus metabolism in the body and recognition of the main role of parathyroid hormone (PTH) in it was slow, throughout the XIX − early XX centuries. Despite the increasing number of observations confirming the development of complications because of hyperfunction of the PG or development of tetany due to their removal, the main link of this relationship remained unidentified for a long time. In view of the unique anatomical features of the PG, they were the last of the endocrine glands found, which the main obstacle was in the rapid study of their functional characteristics. Today, the structure and functions of the PG are described in detail, the manifestations of their various pathological conditions are well studied, and the capabilities of modern medicine allow timely diagnosis and treatment of diseases. The review describes the history of the discovery of the PG, highlights the main stages in the study of their role in calcium-phosphorus metabolism in particular and in the body as a whole, and discusses the prospects for further development in this direction. We analyzed the work devoted to the evolution in the notions of anatomical, physiological, pathological features of the PG.

scholarly journals Heat shock proteins and cardiovascular disease

2018 ◽  
Vol 105 (1) ◽  
pp. 19-37 ◽  
Author(s):  
B Rodríguez-Iturbe ◽  
RJ Johnson
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cell Function ◽  
Molecular Mimicry ◽  
Heat Exposure ◽  
Cross Reactivity ◽  
Immune Reactivity ◽  
Primary Role ◽  
Shock Proteins

The development of stress drives a host of biological responses that include the overproduction of a family of proteins named heat shock proteins (HSPs), because they were initially studied after heat exposure. HSPs are evolutionarily preserved proteins with a high degree of interspecies homology. HSPs are intracellular proteins that also have extracellular expression. The primary role of HSPs is to protect cell function by preventing irreversible protein damage and facilitating molecular traffic through intracellular pathways. However, in addition to their chaperone role, HSPs are immunodominant molecules that stimulate natural as well as disease-related immune reactivity. The latter may be a consequence of molecular mimicry, generating cross-reactivity between human HSPs and the HSPs of infectious agents. Autoimmune reactivity driven by HSPs could also be the result of enhancement of the immune response to peptides generated during cellular injury and of their role in the delivery of peptides to the major histocompatibility complex in antigen-presenting cells. In humans, HSPs have been found to participate in the pathogenesis of a large number of diseases. This review is focused on the role of HSPs in atherosclerosis and essential hypertension.

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