Roles of Heat Shock Proteins in Apoptosis, Oxidative Stress, Human Inflammatory Diseases, and Cancer

Abstract

Heat shock proteins (HSPs) play cytoprotective activities under pathological conditions through the initiation of protein folding, repair, refolding of misfolded peptides, and possible degradation of irreparable proteins. Excessive apoptosis, resulting from increased reactive oxygen species (ROS) cellular levels and subsequent amplified inflammatory reactions, is well known in the pathogenesis and progression of several human inflammatory diseases (HIDs) and cancer. Under normal physiological conditions, ROS levels and inflammatory reactions are kept in check for the cellular benefits of fighting off infectious agents through antioxidant mechanisms; however, this balance can be disrupted under pathological conditions, thus leading to oxidative stress and massive cellular destruction. Therefore, it becomes apparent that the interplay between oxidant-apoptosis-inflammation is critical in the dysfunction of the antioxidant system and, most importantly, in the progression of HIDs. Hence, there is a need to maintain careful balance between the oxidant-antioxidant inflammatory status in the human body. HSPs are known to modulate the effects of inflammation cascades leading to the endogenous generation of ROS and intrinsic apoptosis through inhibition of pro-inflammatory factors, thereby playing crucial roles in the pathogenesis of HIDs and cancer. We propose that careful induction of HSPs in HIDs and cancer, especially prior to inflammation, will provide good therapeutics in the management and treatment of HIDs and cancer.

Cellular calcium and redox regulation: the mediator of vertebrate environmental sex determination?

“…Several authors have proposed a role in TSD for heat shock proteins (HSPs) (Harry, Williams & Briscoe, ; Kohno et al ., ; Bentley et al ., ; Table ). These proteins are chaperones and regulators of transcription factor binding, functions which are essential for maintaining cell function at extreme incubation temperatures (Haslbeck & Vierling, ; Ikwegbue et al ., ).…”

The heat shock protein family geneHspa1lin male mice is dispensable for fertility

“…HSP70s are strong anti-apoptotic proteins which can prevent apoptosis from different stresses, such as heat shock (Durairajanayagam, Agarwal & Ong, 2015), oxidative stress (Ikwegbue et al, 2017), infection (Mays et al, 2019), etc. We applied heat stress to test the anti-apoptotic ability of HSPA1L in testis.…”

“…HSP70s also play a role in cell survival during stresses, including heat shock, oxidative stress, hypoxia, heavy metals, altered pH, inflammation, ischemia, fever, malignancy, etc. (Chen, Feder & Kang, 2018a;Ikwegbue et al, 2017;Radons, 2016;Singh et al, 2010). The changes in expression of HSP70s has been indicated in various diseases, including cancer and nervous system diseases (Lee et al, 2001;Perez et al, 1991;Turturici, Sconzo & Geraci, 2011).…”

Therapeutic potential of Hsp27 in neurological diseases

“…(b) It inhibits the Ask1-JNK pathway leading to cytochrome c leakage [15]. (c) It prevents apoptosome formation [16]. (d) It interacts with Daxx in the nucleus preventing its translocation to cytosol which is essential for interaction with the Fas receptor involving apoptosis [17].…”

“…(e) Hsp27 seems to be involved in inhibition of the Smac from mitochondria, and this may lead to inhibition of caspases [14]. (f) It also downregulates tBID released from caspase 8 [16].…”