HSP

Heat-shock proteins (HSPs), or stress proteins, are highly conserved and present in all organisms and in all cells of all organisms. Selected HSPs, also known as chaperones, play crucial roles in folding/unfolding of proteins, assembly of multiprotein complexes, transport/sorting of proteins into correct subcellular compartments, cell-cycle control and signaling, and protection of cells against stress/apoptosis.

100872-83-1
ML346
100872-83-1
BIX
101714-41-4
Apoptozole
1054543-47-3
1061318-81-7
Debio 0932
1061318-81-7
1134156-31-2
VER-155008
1134156-31-2
HSF1A
1196723-93-9
HSP70-IN-1
1268273-90-0
B0084-007650
KIN1148
1428729-56-9
1454619-14-7
PU-WS13
1454619-14-7
MKT 077
147366-41-4
B0084-470906
KNK437
218924-25-5
30562-34-6
Geldanamycin
30562-34-6
B0084-187070
Celastrol
34157-83-0
467214-20-6
Alvespimycin
467214-20-6
467214-21-7
Alvespimycin HCl
467214-21-7

Background


Heat shock proteins (HSPs) are small polypeptide groups that are classified into families based on molecular weight. HSPs have been classified into several families including small HSPs, HSP40, HSP47, calreticulin, HSP60, HSP70, HSP90 and HSP 100. Within each family are members closely related to each other, but located in different compartments or regulated differently at the expression level. For instance, within the HSP90 family, HSP90 mainly functions in cytosol, while gp96 performs an analogous function in the endoplasmic reticulum (ER). The HSP70 family contains constitutively expressed HSC70 and stress inducible HSP70, both of which are located in the cytosol, whereas Grp78 (Bip) is located in the ER.

Heat shock proteins are expressed by cells in the body as a protection against harmful environmental conditions. HSPs are expressed in situations where cell survival may be compromised. The stimulus for HSP expression includes, but is not limited to: temperature, free radicals, anoxia, bacteria, endotoxin, and viruses. Their expression can be constitutive or inducible depending on the family member. Constitutively expressed members are present in all cell compartments and appear to assist in proper folding and assembly of polypeptide of newly synthesized proteins. Inducible forms were originally described following heat stress; however, a variety of cellular stresses will lead to their induction as part of an orchestrated stress response. Messenger RNAs encoding for HSPs are found in normal conditions, but during stress, transcription of HSP genes occurs rapidly.

HSPs function as a potential cytoprotective protein. Under stressful conditions such as cytotoxic injury, heat shock, oxidative stress, radiation, viral infection, and chemical exposure, HSPs have long been known to serve as protein chaperones in the sense that they assist in protein folding and the correct attainment of functional three-dimensional configuration, while preventing incorrect folding and protein aggregation. While studies that highlight the critical functions of Heat Shock Proteins in various cellular processes have made them an increasing popular subject of interest to medical specialists in a wide variety of fields, including infectious disease, immunology, oncology, and autoimmunity, heat shock proteins are relatively unstudied in the field of endodontics.

Immunological function of HSPs

The immunological function of HSPs was first observed by Srivastava et al. in the study of HSPs in anti-tumor immunity. Mice immunized with tumor derived HSPs rejected the subsequent challenge with the same tumor. Whereas normal tissue derived HSPs did not protect mice from tumor challenge. This has been verified in a series of studies using gp96, HSP70, HSP90, calreticulin, HSP110 and GRP 170 (21-25). HSP-mediated tumor specific immunogenicity is dependent on CD8+ T cells and macrophages in the priming phase, and on CD4+, CD8+ T cells and macrophages in the effector phase. Preparation of HSPs from a tumor was associated with peptides derived from the tumor specific antigens (Ags). Thus it has been proposed that HSPs function as Ag chaperones to channel peptides into APCs and induce T cell activation. Consistent with this proposition, HSP peptide complexes reconstituted in vitro can elicit Ag-specific CD8+ T cell responses.

Another line of evidence supporting the immunogenicity of HSPs comes from the study of the effects of fever-range hyperthermia on immune responses. Hyperthermia increases trafficking of effector cells to the site of inflammation, accelerates migration of Langerhans’ cells to the draining lymph nodes and promotes an Ag-specific T cell response. Given the fact that hyperthermia induces expression of HSPs, the up-regulation of immune response by hyperthermia highly indicates the immunological functions of HSPs.

References:

Zheng, Hong. "Heat shock proteins in dendritic cell activation and antigen cross-presentation." (2003).

Goodman, Steven Chad. The role of heat shock proteins in periapical disease. Diss. The University of Texas School of Dentistry at Houston, 2013.