Hsp70 in Redox Homeostasis

Abstract

Cellular redox homeostasis is precisely balanced by generation and elimination of reactive oxygen species (ROS). ROS are not only capable of causing oxidation of proteins, lipids and DNA to damage cells but can also act as signaling molecules to modulate transcription factors and epigenetic pathways that determine cell survival and death. Hsp70 proteins are central hubs for proteostasis and are important factors to ameliorate damage from different kinds of stress including oxidative stress. Hsp70 members often participate in different cellular signaling pathways via their clients and cochaperones. ROS can directly cause oxidative cysteine modifications of Hsp70 members to alter their structure and chaperone activity, resulting in changes in the interactions between Hsp70 and their clients or cochaperones, which can then transfer redox signals to Hsp70-related signaling pathways. On the other hand, ROS also activate some redox-related signaling pathways to indirectly modulate Hsp70 activity and expression. Post-translational modifications including phosphorylation together with elevated Hsp70 expression can expand the capacity of Hsp70 to deal with ROS-damaged proteins and support antioxidant enzymes. Knowledge about the response and role of Hsp70 in redox homeostasis will facilitate our understanding of the cellular knock-on effects of inhibitors targeting Hsp70 and the mechanisms of redox-related diseases and aging.

Overexpression of Heat Shock Protein 70 Ameliorates Meat Quality of Broilers Subjected to Pre-Slaughter Transport at High Ambient Temperatures by Improving Energy Status of Pectoralis Major Muscle and Antioxidant Capacity

“…In addition, the adaptive responses of broilers to pre-slaughter transport stress were insufficient, as the activities of antioxidant enzymes, including T-AOC, T-SOD, and GSH-Px, remained unchanged, which is in accordance with the findings obtained by Liao et al [ 40 ]. HSP70 exerts its cytoprotective effect by facilitating the degradation of damaged oxidized proteins via the ubiquitin-proteasome system, as well as by inducing the expression of key antioxidant enzymes and adjusting their activities under oxidative stress [ 41 ]. According to Gu et al [ 14 ], HSP70 significantly elevated antioxidant enzyme activities and inhibited lipid peroxidation to protect the intestinal mucosa of broilers from heat-stress injury.…”

Heat-Induced Proteotoxic Stress Response in Placenta-Derived Stem Cells (PDSCs) Is Mediated through HSPA1A and HSPA1B with a Potential Higher Role for HSPA1B

“…Protein structural maintenance and stability is an outcome of the intermolecular and intramolecular interactions. Anything potentially disturbing these interactions, such as temperature, oxidative stress, and heavy metals, is a proteotoxic stressor and leads to protein misfolding and potentially aggregation [ 20 , 40 , 41 , 42 ]. We confirmed the presence of proteotoxic stress by measuring proteome aggregation and cell proliferation, and validated the dose-response nature of stress by monitoring the Hsp70 gene expression.…”

Antioxidant Molecular Brain Changes Parallel Adaptive Cardiovascular Response to Forced Running in Mice

“…We analyzed the proteasome components 19S and 20S. The lack of changes in protein levels of the regulatory cap component 19S proteasome and in the proteolytic signaling hub HSP70 [ 64 ] suggests that the effects were at the level of the catalytic 20S proteasome or immunoproteasome. We found an increase in trypsin-like enzymatic activity in the cerebral cortex, whereas other authors have reported also increases in chymotrypsin-like and caspase-like enzymatic activities in the hippocampus of mice submitted to voluntary wheel running [ 65 ].…”