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Stress responses in biology and medicine: Stress of life in molecules, cells, organisms, and psychosocial communities (Annals of the New York Academy of Sciences 1113, (304-310))
... These studies, which have used primarily 17-allylamino-17-demethoxy-geldanamycin (17AAG) (Figure 1), a GM derivative with a more favorable profile, but also synthetic small molecule Hsp90 inhibitors, clearly demonstrate that Hsp90 inhibitors possess potent anti-cancer activity at nontoxic doses101112. Several models have been proposed to explain the selective sensitivity of cancer cells to Hsp90 inhibition13141516. One model, akin to the 'oncogene addiction' model proposed by Weinstein [13], focuses on the exclusive dependence of some transformed cells on a sensitive Hsp90 client protein. ...
... Unfortunately, only limited animal studies have been performed with these inhibitors to date and, therefore, the ability of 17AAG or other Hsp90 inhibitors to degrade most putative Hsp90 clients in vivo has yet to be explored in relevant animal model systems. A complementary 'Hsp90 addiction model' is based upon the hypothesis that Hsp90 is limiting in many tumor cells because of their increased load of mutated and unfolded proteins [14,15]. An increased requirement for Hsp90 chaperone function in tumors cells may be due to the overexpression of mutated Hsp90 clients or amplification of clients such as HER2. ...
... This may explain why therapies that further stress the chaperone system such as anti-angiogenic agents, proteasome inhibitors, cytotoxic chemotherapies, and radiation may broadly synergize with Hsp90 inhibitors even in tumors in which Hsp90 inhibitors alone have little or no activity123. Finally, the selective sensitivity of transformed cells for Hsp90 inhibitors may be partly due to the selective accumulation of these drugs in cancer cells [15]. The selective accumulation of Hsp90 inhibitors in tumors has been reported with compounds that display little structural homology and diverse solubility profiles. ...
Heat shock protein 90 has emerged as an important target in several diseases. The present review will discuss our understanding of the role played by Hsp90 in regulating and maintaining the transformed phenotype in cancers and neurodegenerative diseases, as well as recent findings on its roles in fungal and viral infections. It will also update the reader on the preclinical development and clinical translation of Hsp90 inhibitors.
... Sport scientists were not the only professionals to apply the lessons of the GAS to their work (Csermely, Korcsmaros, & Sulyok, 2007;Gellman & Turner, 2013;Lovallo, 2005). More specifically, physicians and other licensed healthcare professionals also saw Seyle's theory as quite helpful in explaining many conditions among the individuals under their care. ...
... More specifically, physicians and other licensed healthcare professionals also saw Seyle's theory as quite helpful in explaining many conditions among the individuals under their care. To illustrate, many of the chronic diseases seen in contemporary Western society are manifestations of the Stage of Exhaustion of the GAS, in which the tissue or system has become overly fatigued and/or lost its ability to adapt to the stresses regularly placed upon it (Csermely et al., 2007). Conditions such as congestive heart failure, kidney failure, herniated disks, torn rotator cuffs, ruptured anterior cruciate ligaments (ACL), and psychological depression are but a few examples of diseases or injuries that may arise out of the third stage of the GAS (Gellman & Turner, 2013). ...
Background: Exercise prescription and training progression for competitive athletes has evolved considerably in recent decades, as strength and conditioning coaches increasingly use periodization models to inform the development and implementation of training programs for their athletes. Similarly, exercise prescription and progression is a fundamental skill for sport physical therapists, and is necessary for balancing the physiological stresses of injury with an athlete’s capacity for recovery. Objective: This article will provide the sport physical therapist with an overview of periodization models and their application to rehabilitation.
Summary: In recent decades models for exercise prescription and progression also have evolved in theory and scope, contributing to improved rehabilitation for countless athletes, when compared to care offered to athletes of previous generations. Nonetheless, despite such advances, such models typically fail to fully bridge the gap between such rehabilitation schemes and the corresponding training models that coaches use to help athletes peak for competition. Greater knowledge of these training systems, also known as periodization models, can help sport physical therapists in their evaluation, clinical reasoning skills, exercise progression, and goal setting for the sustained return of athletes to high level competition.
... Heat shock-or stress induced activation of a set of heat shock protein genes is a characteristic of eukaryotic and prokaryotic cells. The heat shock proteins have been implicated as chaperons for protein folding and transport282930. Heat shock proteins fall into several subfamilies, the low molecular weight (16–35 kDa) or small heat shock proteins (smHsps), the hsp60 family, the hsp70 family (68–78 kDa), and the high molecular weight (89–110 kDa) heat shock protein families (hsp90 and hsp100) [28, 29]. ...
Glycoproteins are involved in many important molecular recognition processes including invasion, adhesion, differentiation, and development. To identify the glycoproteins of Toxoplasma gondii, a proteomic analysis was undertaken. T. gondii proteins were prepared and fractioned using lectin affinity chromatography. The proteins in each fraction were then separated using SDS-PAGE and identified by tryptic in gel digestion followed by tandem mass spectrometry. Utilizing these methods 132 proteins were identified. Among the identified proteins were 17 surface proteins, 9 microneme proteins, 15 rhoptry proteins, 11 heat shock proteins (HSP), and 32 hypothetical proteins. Several proteins had 1-5 transmembrane domains (TMD) with some being as large as 608.3 kDa. Both lectin-fluorescence labeling and lectin blotting were employed to confirm the presence of carbohydrates on the surface or cytoplasm of T. gondii parasites. PCR demonstrated that selected hypothetical proteins were expressed in T. gondii tachyzoites. This data provides a large-scale analysis of the T. gondii glycoproteome. Studies of the function of glycosylation of these proteins may help elucidate mechanism(s) involved in invasion improving drug therapy as well as identify glycoproteins that may prove to be useful as vaccine candidates.
According to the cognitive activation theory of stress (CATS), a formal system of systematic definitions, the term "stress" is used for stress stimuli, the stress experience, the nonspecific, general stress response, and the experience of the stress response. The stress response is normal, healthy, and necessary alarm. If sustained there may be a risk of illness and disease. The level and duration of the alarm depend on the expectancy of the outcome of stimuli and the specific responses available for coping. The most common health complaints are subjective health complaints like muscle pain, tiredness and mood changes. These are normal aches of short duration and low intensity for most people. For some the pains and complaints are substantial and longlasting with serious implications for functioning. There are no sharp or obvious limits in the distribution of health complaints, separating "normal" and endurable pain and complaints, and intolerable complaints that need professional help. These conditions are most often unspecific, and are the most common reason for encounters with health professionals, and the most frequent reason for sick leave and disability. There is a striking comorbidity for all these conditions. This may be explained by psychobiological sensitization within neural loops, maintained by sustained activation, which has been suggested as a mechanism for these conditions.