Endogenous Extracellular Hsp72 Release Is an Adaptive Feature of the Acute Stress Response

Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72

“…In fact, glial cells [88], B cells [89], tumor cells [64], and human peripheral blood mononuclear cells (PBMC) [90] have been shown to exocytotically release eHsp72 in the absence of detectable cell death. Furthermore, numerous whole organism stressors have been observed to elevate circulating eHsp72 [82,91], often within 10 -25 min of stressor onset, a speed that suggests the classic protein induction/ necrosis release pathway is not likely. Circulating eHsp72 also increases in response to stressors, which are unlikely to result in large necrotic cell death such as following conditioned contextual fear, predatory stress, and exercise stress (described in ref.…”

“…Not long after these reports, we [77][78][79] and Febbraio et al [80,81] reported that organisms in the absence of clinical disease states also rapidly increase the concentration of eHsp72 in blood after exposure to acute physical and/or psychological stressors. These papers were the first to demonstrate that an increase of eHsp72 in the blood occurs in healthy organisms after exposure to acute stressors and led us to suggest that stress-induced eHsp72 release may be a previously unrecognized feature of the normal stress response [82].…”

“…The current review will focus on endogenous eHsp72, as stress-induced release of eHsp72 into the blood has only recently been documented, and little is understood about its unique mechanism(s) of induction/release and its powerful in vivo immunological function(s). Understanding more about the stress-induced eHsp72 response is important because the function of in vivo endogenous eHsp72 is likely context-dependent, such that in a normal physiological state, eHsp72 facilitates immunity [82], whereas in a pathophysiological state, eHsp72 exacerbates inflammatory diseases (e.g., atherosclerosis, Alzheimer's, inflammatory bowel disease) [83]. This idea requires additional investigation because depending on the circumstances, eHsp72 can also stimulate anti-inflammatory cytokines [59,67,69].…”

Acute isoproterenol induces anxiety-like behavior in rats and increases plasma content of extracellular vesicles

“…In particular, an increase of Hsp70 was seen in cardiomyocytes of rodents exposed to forced exercise and β-adrenergic activation or cardiac hypertrophy induced by isoproterenol [40,41]. Different studies report an increase of circulating Hsp70 level after psychological stress and physical stress [14,15,42] linked to an increase of blood corticosterone level [43]. Recent studies show that Hsp70 can be released in extracellular medium in an exosome-dependent manner [16,17].…”

“…To investigate a possible stress condition induced by isoproterenol, with consequent involvement of glucocorticoids in the anxiety-like behavior, plasma corticosterone level was evaluated. An increase of heat shock protein 70 (Hsp70) plasma level has also been associated with a stress condition [14,15]; moreover, Hsp70 is mainly released inside EVs [16,17]. Therefore, EV content of Hsp70 was detected.…”