Does Hsp60 Provide a Link between Mitochondrial Stress and Inflammation in Diabetes Mellitus?

Abstract

The focus of this review is to summarise the known relationships between the expression of heat shock protein 60 (Hsp60) and its association with the pathogenesis of Type 1 and Type 2 diabetes mellitus. Hsp60 is a mitochondrial stress protein that is induced by mitochondrial impairment. It is known to be secreted from a number of cell types and circulating levels have been documented in both Types 1 and 2 diabetes mellitus patients. The biological significance of extracellular Hsp60, however, remains to be established. We will examine the links between Hsp60 and cellular anti- and proinflammatory processes and specifically address how Hsp60 appears to affect immune inflammation by at least two different mechanisms: as a ligand for innate immune receptors and as an antigen recognised by adaptive immune receptors. We will also look at the role of Hsp60 during immune cell activation in atherosclerosis, a significant risk factor during the pathogenesis of diabetes mellitus.

Tandem Affinity Purification and Nano HPLC-ESI-MS/MS Reveal Binding of Vitamin D Receptor to p53 and other New Interaction Partners in HEK 293T Cells

“…HSP60 is involved in the prevention of heat-induced protein damage and the transportation and refolding of cellular proteins from the cytoplasm into the mitochondrial matrix (29; 30). Additionally, studies have indicated a role of HSP60 in several disorders where the relevance of the vitamin D endocrine system has been discussed, including stress response, diabetes, cancer and certain types of immunological disorders (30)(31)(32)(33). It can be speculated that HSP60 may be involved in the putative transportation of VDR from cytoplasm to mitochondrial matrix.…”

Peer Review #3 of "Application of built-in adjuvants for epitope-based vaccines (v0.1)"

“…Manuscript to be reviewed Heat shock proteins (HSPs) are a type of cellular companion protein produced by biological cells that are stimulated by environmental stressors and can be divided into several families, each of which is composed of different members (Juwono & Martinus, 2016;Craig, 2018;Pearl et al, 2008;Tang et al, 2005;Bolhassani & Rafati, 2008) (Table 3). HSPs can be internalized by APCs through receptor-mediated endocytosis and can also promote the activity of some cytokines, chemokines, and co-stimulatory molecules through the NF-B signaling pathway, since HSPs are the molecular chaperones of the antigen epitopes in the APC-MHC I delivery pathway (Robert, 2003;Zachova et al, 2016).…”

Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor

“…On the other hand, serum HSP60 has been recognized as a potent inductor of proinflammatory mediators in various cells indulging innate immune cells, skeletal muscle, cardiomyocytes, and adipocytes [11,[15][16][17]. Furthermore, the high levels of serum HSP60 have been found in the individuals with adjuvant arthritis and atherosclerosis [18,19].…”

“…Currently, accumulating evidences have linked HSP60 with diabetes mellitus and diabetic complications, although the molecular mechanisms are poorly understood [18][19][20]. For instance, serum HSP60 levels have been found to be significantly elevated in the patients with type 2 diabetes and morbid obesity, due to enhanced mitochondrial stress and responsible for inflammation [20][21][22].…”