Immunopathology
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Much attention has recently focused on the family of heat shock proteins (hsps, see Chapter 8). These entities are some of the most conserved proteins throughout evolution. They are produced by virtually all living cells in response to physical or chemical stress, they are made by organisms infecting humans, and by human cells which are infected and which fight infection. Many of these molecules are chaperones, they bind to various proteins within the cell and help to determine their proper conformation; chaperones also direct proteins and peptides through the various intracellular compartments. Microbial hsps are dominant antigens in immune responses, particularly in mycobacterial infections. Since these proteins are highly conserved, it is inevitable that self hsps share epitopes with microbial hsps. It seems that immune responses to microbial hsps must activate clones which are also self-reactive. The distinction between protective anti-microbial immunity directed against hsps versus pathogenic self-reactive immunity against cross-reactive self-hsps is quite unclear at present.
Caenorhabditis elegans Aging is Associated with a Decline in Proteostasis
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Similarly, another targeted study was performed to identify the entire complement of molecular chaperones that are required to maintain proteostasis even when the misfolded protein load is abnormally high due to the presence of neurodegenerative disease-associated proteins. All 332 known or presumptive molecular chaperones were targeted for gene knock down in C. elegans by RNAi. This was done both in Aβ3-42 animals and in animals expressing expanded polyQ-YFP in body wall muscle cells. As evidence that the collection of proteostasis regulators identified in screens described here are starting to approach saturation, the CCT chaperonin complex as well as Hsp90, two Hsp90 co-chaperones (sti-1 and cdc-37), and two DnaJ chaperones (dnj-8 and dnj-12) that likely act as Hsp70 co-chaperones were identified [86]. Nonetheless, additional targeted screens continue to be performed, mostly to determine whether specific disease-associated proteins interact with unique subsets of the proteostasis machinery.
Responses to Muscular Exercise, Heat Shock Proteins as Regulators of Inflammation, and Mitochondrial Quality Control
Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse in The Routledge Handbook on Biochemistry of Exercise, 2020
Broadly defined, molecular chaperones are a key set of proteins that help “guide” various proteins within the cell to remain functional and/or get targeted for degradation under stressful conditions. In this way, molecular chaperones such as HSPs allow cells to survive under stress. HSPs specifically facilitate the folding of new proteins, the refolding of damaged proteins, the targeting on non-functional proteins/organelles for degradation, intracellular signalling, and the import/export of proteins into/out of the mitochondria (Figure 7.1) (15, 24, 29, 92). Importantly, different HSPs (characterized by their molecular weight in kilodaltons) have varying functions. For the purposes of this chapter, we will focus on four well-characterized HSP families: HSP70, HSP40, HSP90, and HSP25.
Guarana (Paullinia cupana Mart.) protects against amyloid-β toxicity in Caenorhabditis elegans through heat shock protein response activation
Published in Nutritional Neuroscience, 2020
Daniele Coradini Zamberlan, Leticia Priscilla Arantes, Marina Lopes Machado, Tassia Limana da Silveira, Aline Franzen da Silva, Ivana Beatrice Mânica da Cruz, Claudia Pinto Figueiredo, Félix Alexandre Antunes Soares
Caenorhabditis elegans is a free living nematode that offers an alternative complementary system for deciphering neurodegenerative etiologies and aiding in drug discovery.13 This powerful model organism presents advantages in relation to conventional models, including a rapid generation time, short lifespan, and a simple nervous system.14 Human Aβ protein expression in C. elegans results in protein aggregation, leading to a progressive paralysis phenotype.15 Previous studies have suggested that Aβ-induced toxicity in C. elegans can be blocked by the conserved heat-shock transcription factor orthologue hsf-1, which functions as a transcriptional regulator of stress-induced gene expression and whose activity is required for the heat-shock and proteotoxicity responses.16 In fact, dysfunctional chaperone activity has been related to age-dependent diseases, such as AD.17 However, little is known about how to effectively control protein misfolding and prevent aggregation by targeting chaperone activity in neurodegenerative diseases.
Hydrogen deuterium exchange mass spectrometry applied to chaperones and chaperone-assisted protein folding
Published in Expert Review of Proteomics, 2019
Florian Georgescauld, Thomas E. Wales, John R. Engen
Many chaperones, but not all, are known as heat-shock proteins (Hsp) because they are overexpressed by cells under conformational stress conditions, such as exposure to high temperature or oxidative conditions. They can be classified according to their molecular weight (e.g., Hsp40 is a Hsp with a molecular weight of ~40 kDa), and the common chaperones include Hsp40, Hsp60, Hsp70, Hsp90, Hsp100, and the ‘small’ heat shock proteins known as sHsp’s. More than 30 classes of chaperones, different in sequence and mechanism of action, are known to date. Except sHsps, chaperones are ATP-dependent protein machines, highly regulated, and form a network whose main function is to insure correct cellular proteostasis. Figure 1 shows the three main chaperone families: Hsp60, Hsp70, and Hsp90.
High altitude hypoxia on brain ultrastructure of rats and Hsp70 expression changes
Published in British Journal of Neurosurgery, 2019
Wen-Hua Li, Yu-Xiang Li, Jun Ren
Heat shock response is a kind of cellular level biological response to stress. Since heat shock response was found by Tissiéres et al.1 in the study on Drosophila larvae in 1974; heat shock response has become a hot research topic in various fields. The product of heat shock response was heat shock protein (HSP), while the first gene to be cloned and identified was HSP70. The human HSP70 gene is located in chromosome 1, 5, 6, 9, 11 and 14; and also considered to be present in chromosome 21.2,3 Their common code of a set of relative molecular mass from 66,000 to 78,000 was highly related to the protein. HSP70 gene family members can be used as a molecular chaperone to promote the correct folding, assembly and transport of new synthetic proteins, and promote the re-folding or degradation of proteins4,5. HSP70 protein plays an important protective role in the formation of heat tolerance or poison tolerance, as well as the prevention of oxidative damage. Heat stress protein is very important for the stability and adaptability of the intracellular environment. It is known that nucleotide substitution, deletion or insertion mutations can adjust the start of function or transcriptional activity6, while different HSP70 expression levels can modulate stress, or disease susceptibility or tolerance.7 Therefore, this study aimed to observe changes in brain tissue and HSP70 expression in high-altitude hypoxia rats, in order to clarify the mechanism of HSP70 in high-altitude hypoxia adaptation.
Related Knowledge Centers
- DNA
- Histone
- Molecular Biology
- Protein
- Protein Folding
- Proteolysis
- Nucleosome
- Heat Shock Protein
- Steric Effects
- Translation