Heat Shock Proteins in the Regulation of the Apoptotic Response

摘要: Cell growth, differentiation and death are highly regulated events during the normal development of cells. Following pioneering work Kerr [1], it has become apparent that dying eukaryotic cells can undergo two fundamentally different types death, necrosis or accidental cell apoptosis programmed death. Apoptosis, unlike necrosis, occurs through activation a cell-intrinsic cascade which be modulated by many exogenous signals. The undergoes relatively ordered form characterised morphologically cytoplasmic shrinkage, cellular crenation, nuclear margination condensation, internucleosomal DNA fragmentation ~nally formation apoptotic bodies [2–5]. A critical part is ef~cient recognition removal these tissue macrophages without an in_ammatory response [6]. This involves rearrangement biochemical alteration plasma membrane in aiding [7]. mechanism prevents release cytotoxic contents proin_ammatory limits possibility neighbouring host injury [8]. process distinct from lysis where their into surrounding tissues perpetuate local response. Apoptosis plays essential homeostasis with important roles embryological remodelling, in_ammation, immune tolerance [2,9,10]. Dysregulated associated variety human diseases, including cancer, autoimmunity, viral infections, allergic disorders neurodegenerative diseases [5,11,12]. Heat shock proteins (HSPs) stress found all species thought to play protective role under [13,14]. Recent evidence supports for HSPs modulating cell’s stimulus. In general, have been shown protect inducing signal [15]. Cells exposed ever increasing increments noxious stressor respond generally graded manner [16]. Low levels appear induce altering biochemistry promote survival at environmental otherwise may lethal cell. resistance kinetically linked synthesis [17]. When removed continue function normally HSP return normal. As increase damage exceeds ability triggered. At extremes no longer capable controlling its fate, degenerative becomes predominant view universal effect has, however, recently come challenge revelation can, depending on type stimulus evoked, increased [18,19,20]. better understanding heat response, speci~c regard HSPs, provide insight regulation suggest paradigms therapeutic interventions dysregulated occurs.