Regulation of apoptosis by heat shock proteins

Abstract

Thermotolerance, the acquired resistance of cells to stress, is a well-established phenomenon. Studies of the key mediators of this response, the heat shock proteins (HSPs), have led to the discovery of the important roles played by these proteins in the regulation of apoptotic cell death. Apoptosis is critical for normal tissue homeostasis and is involved in diverse processes including development and immune clearance. Apoptosis is tightly regulated by both proapoptotic and antiapoptotic factors, and dysregulation of apoptosis plays a significant role in the pathophysiology of many diseases. In the recent years, HSPs have been identified as key determinants of cell survival, which can modulate apoptosis by directly interacting with components of the apoptotic machinery. Therefore, manipulation of the HSPs could represent a viable strategy for the treatment of diseases. Here, we review the current knowledge with regard to the mechanisms of HSP-mediated regulation of apoptosis.

Theory about the Embryo Cryo‐Treatment

“…Compared to the pregnancies following thawed cleavage ET, thawed blastocyst ET was associated with a 14% higher risk of miscarriage 4. It is well known that stress signals, if moderate, are able to inhibit multiple apoptotic pathways 12, 13. The authors suggest that, because of the detoxified effect and rising activity of the trophectodermal cells after freezing or thawing, implantation will initiate more aneuploidy blastocysts.…”

Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol

“…In addition to mitigating against protein misfolding and aggregation, Hsps carry out a number of other neuroprotective functions that include inhibiting apoptosis (Kennedy et al 2014), as well as protecting the functional integrity of synapses (Karunanithi et al 1999(Karunanithi et al , 2002Asea and Brown 2008;Brown 2008;Karunanithi and Brown 2015), which are adversely affected in early stages of neurodegenerative diseases (Masliah et al 2001;Scheff et al 2006;Milnerwood and Raymond 2010;Stephan et al 2012;Chung et al 2015;Wu et al 2015). Functional activities of Hsps, such as protein refolding (Fan et al 2003;Goloubinoff and De Los Rios 2007;Mayer 2013;Mattoo and Goloubinoff 2014;Dekker et al 2015) and disruption of protein aggregates (Nillegoda and Bukau 2015;, require co-operation between several different classes of Hsps.…”

Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression

“…Protein damaging stress, including hyperthermia, can lead to apoptosis through BAX activation, mitochondrial release of cytochrome c, and caspase activation, although the molecular mechanisms responsible for BAX activation in heat-stressed cells are unclear (15,16). Sublethal exposure to hyperthermia induces the expression of molecular chaperone proteins, such as HSP70, which can inhibit apoptosis (17,18).…”