Roles of Heat Shock Proteins in Apoptosis, Oxidative Stress, Human Inflammatory Diseases, and Cancer - PubMed (original) (raw)
Review
Roles of Heat Shock Proteins in Apoptosis, Oxidative Stress, Human Inflammatory Diseases, and Cancer
Paul Chukwudi Ikwegbue et al. Pharmaceuticals (Basel). 2017.
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.
Keywords: apoptosis; cancer; heat shock proteins; inflammation; reactive oxygen species; tumour necrosis factor-α.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Figure 1
Model proposing the roles of heat shock proteins in HIDs and cancer. The above model represents the proposed roles that heat shock proteins play in human inflammatory diseases and cancer. (1) the onset of the stress signal; (2) stress activates inflammatory reactions which aims at repairing the damage caused by the stress; (3) generation of ROS from the infected area; (4) activation of the heat shock factor-1 (HSF-1), which increases the synthesis of the cytoprotective heat shock proteins; (5) activation of heat shock proteins; (6) stress, as well as inflammation and heat shock proteins, activate the immune response and form part of the innate immune response (7); cytoprotective heat shock proteins inhibit further generation of ROS, as well as inflammation, thus blocking excessive ROS and inflammation mediated-apoptosis via the inhibition of pro-inflammatory and pro-apoptotic factors; (9) excessive apoptosis mediated by ROS; (8) accumulated level of ROS leading to oxidative stress; (10) immune response, inflammatory reaction, accumulated ROS level and excessive apoptosis mediated by ROS as a result of antioxidant suppression, leading to oxidative stress and chronic inflammation marked with massive cellular and tissue destruction; and (11) long-term uncontrolled chronic inflammation degenerates to HIDs and cancer.
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