Heat Shock Protein 70 (HSP70) Protein-Protein Interactions and a Putative Mechanism for the Potential Benefits of Heat Therapy for Type 2 Diabetes Mellitus

Abstract

The use of heat therapy to treat diseases was very common in Africa. To date, the number of people using this form of therapy is very much on the decrease. Data on the molecular action mechanisms of how it might induce beneficial effects remain unknown. The aim of the present study was to make a contribution towards understanding the putative implication of Heat Shock Protein 70 (HSP70) in the pathophysiology of Type 2 Diabetes Mellitus (T2DM) and the hypothetical benefits of heat therapy through the establishment of a network of protein-protein interactions between Kruppel Like Factor 14 (KLF14), Transcription Factor 7 Like 2 (TCF7L2), Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and HSP70 (HSPA4). Data were generated by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software version 10.0. This was used to identify the known and predicted protein-protein interactions (including direct or physical and indirect or functional associations) in the KLF14, TCF7L2, PPARG and HSP70 protein networks. With the active prediction methods (Gene Fusion, Neighborhood, Co-occurrence, Co-expression, Experiments, Databases and Text Mining) as interaction sources, Medium Confidence (0.400) and maximum number of interactions were used to show no more than 50 at the first shell and none at the second shell parameters. Fifty (50) proteins were identified to interact with these four proteins, namely KLF14, TCF7L2, PPARG and HSP70, resulting in a network diagram with 54 nodes (gene/proteins) and 485 edges, representing protein-protein associations. The network showed that HSP70 strongly interacts with other heat shock proteins like HSP90. The HSPBP, a cytoplasmic co-chaperone 1, inhibits HSPA1A chaperone activity by changing the conformation of its ATP-binding domain, thus interfering with this function. Based on the data generated by this in silico study, the potential beneficial effects of heat therapy on T2DM could probably be coordinated by the HSP70 protein-protein interactions involved in cell life and in the susceptibility to T2DM.