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 Krüppel 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 <i>in silico</i> 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.
Highlights
Type 2 Diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia and perturbations in protein, lipid and carbohydrate metabolism due to defects in insulin sensitivity and/or insulin resistance, which result in Magellan Guewo-Fokeng et al.: Heat Shock Protein 70 (HSP70) Protein-Protein Interactions and a Putative
Fifty proteins (CTNNB1, STIP1, PPARGC1A, MED1, NCOA1, EP300, HSP90AA1, HIF1A, STUB1, UBC, BAG1, NCOR1, DNAJB1, NCOA2, HDAC3, BAG3, TP53, LEP, ADIPOQ, CTBP1, NCOR2, GRPEL2, SLC2A4, SNCA, GRPEL1, CD36, NCOA6, KLF4, NCOA3, PARK2, ESR1, CREBBP, TLE1, PLIN1, Transforming Growth Factor Beta 1 (TGFB1), AXIN2, TLE4, JUP, GCG, TLE2, NLK, PCK1, IL4, SP1, CLPB, SUMO1, HSPBP1, T, IL2, DKK1) were identified to interact with these four proteins (KLF14, Transcription Factor 7 Like 2 (TCF7L2), Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and HSP70). This resulted in a network diagram with 54 nodes and 485 edges or interactions (Figure 1). This diagram was built from two proteins/genes mainly implicated in T2DM and obesity, one master gene for T2DM and obesity, and HSP70
In 2003, Zouari and collaborators carried out a study on obese Tunisians which suggested that HSP70-2 polymorphism has susceptibility implications in both obesity and T2DM [19]
Summary
Type 2 Diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia and perturbations in protein, lipid and carbohydrate metabolism due to defects in insulin sensitivity and/or insulin resistance, which result in Magellan Guewo-Fokeng et al.: Heat Shock Protein 70 (HSP70) Protein-Protein Interactions and a PutativeMechanism for the Potential Benefits of Heat Therapy for Type 2 Diabetes Mellitus severe acute and chronic complications [1]. The World Health Organization (WHO) noted that the global number of malaria cases fell from an estimated 262 million in 2000 to 229 million in 2019, though still high [11]. This drop could be attributed to the use of Intermittent Preventive Treatment (IPT) by pregnant women, a great variety of Artemisinin-based Combination Therapies (ACTs) and other drugs, and lastly, vector control strategies such as the use of long lasting Insecticide-Treated Nets (ITNs) and indoor residual sprays [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
