The role of heat shock proteins in gastrointestinal diseases.
Heat shock proteins (HSPs) are a highly conserved family of proteins which inhabit almost all subcellular locations and cellular membranes. Depending on their location, these proteins perform a variety of chaperoning functions including folding of newly synthesised polypeptides. HSPs also play a major role in the protection of cells against stressful and injury-inciting stimuli. By virtue of this protective function, HSPs have been shown to prevent acinar cell injury in acute pancreatitis. Also, the levels of HSPs have been shown to be markedly elevated in various forms of cancers when compared with non-transformed cells. Further, inhibition of HSPs has been shown to induce apoptotic cell death in cancer cells suggesting that inhibition of HSPs has a potential to emerge as novel anti-cancer therapy, either as monotherapy or in combination with other chemotherapeutic agents. Several studies have suggested that HSPs can interact with and inhibit both intrinsic and extrinsic pathways of apoptosis at multiple sites. Besides the anti-apoptotic role of HSPs, recent studies suggest that they play a role in the generation of anti-cancer immunity, and attempts have been made to utilise this property of HSPs in the generation of anti-cancer vaccines. The anti-apoptotic function and mechanism of various subtypes of HSPs as well as the current status of anti-HSP therapy are discussed in this review.
Dudeja
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Division of Basic and Translational Research, Department of Surgery, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Vickers
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Saluja
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AK
D017209:Apoptosis; D004789:Enzyme Activation / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000209:etiology / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects
D006360:Heat-Shock Proteins