Heat shock proteins and molecular chaperones: implications for adaptive responses in the skin

Recent advances in the biology of heat-shock proteins (hsps) are reviewed. These abundant and evolutionarily highly conserved proteins (also called stress proteins) act as molecular escorts. Hsps bind to other cellular proteins, help them to fold into their correct secondary structures, and prevent misfolding and aggregation during stress. Cytoplasmic hsp70 and hsp60 participate in complicated protein-folding pathways during the synthesis of new polypeptides. Close relatives of hsp70 and hsp60 assist in the transport and assembly of proteins inside intracellular organelles. Hsp90 may have a unique role, binding to the glucocorticoid receptor in a manner essential for proper steroid hormone action. Hsps may also be essential for thermotolerance and for prevention and repair of damage caused by ultraviolet B light. A unique class of T lymphocytes, the gamma delta T cells, exhibits a restricted specificity against hsps. These T cells may constitute a general, nonspecific immune mechanism directed against the hsps within invading organisms or against very similar hsps within invading organisms or against very similar hsps expressed by infected (stressed) keratinocytes. Immunologic cross-reactivity between hsps of foreign organisms and of the host may play a role in some autoimmune diseases. Although hsps are expressed in the skin, many questions remain about their role during injury, infection, and other types of cutaneous pathophysiology.     

Heat shock proteins of Toxoplasma gondii

We have investigated heat shock protein (HSP) expression in mouse-virulent and -avirulent strains of Toxoplasma gondii by performing Western blot analysis using a monoclonal antibody against HSP65 of Mycobacterium bovis and a polyclonal antiserum against HSP70 of Plasmodium falciparum as primary antibodies. We initially observed that murine macrophages express HSP65 when infected with either virulent or avirulent strains, a result which contradicts previous reports. Differential HSP expression consistent which virulence was observed between strains, with high levels of a 70kDa HSP (HSP70) only detected in virulent strains in vivo. This protein was not observed in virulent strains in the immunocompromised mouse or in vitro, suggesting induction by immunological stress. This protein was only poorly expressed in avirulent strains. A 65kDa protein was observed in all strains in vivo and in vitro, suggesting a shared epitope with HSP70. These results are consistent with the hypothesis that the induced expression of HSP70 in virulent strains of T. gondii by immunological stresses may provide protection for these strains against cell damage associated with invasion of the host, allowing the virulent strains to persist as tachyzoites without the requirement for the encystation observed in avirulent strains.     

Heat shock proteins: regulators of stress response and apoptosis

Nup153 is a large O-linked glycoprotein that is a component of the basket-like structure that forms the nucleoplasmic face of nuclear pore complexes (NPCs). The Nup153 molecule has a tripartite structure consisting of N- and C-terminal domains flanking a central zinc finger domain. All of the targeting and assembly information contained within Nup153 is contributed by the N-domain. In fact this region of the molecule can target a cytosolic protein, pyruvate kinase, to the nucleoplasmic face of the NPC. The zinc finger and C-terminal domains appear to have no role in these targeting and assembly activities. Deletion analysis reveals that there are two distinct regions within the Nup153 N-domain that contain different targeting functions. One of these is directly involved in assembly into the NPC while a second overlapping region may target Nup153, as well as other reporter molecules, to the inner face of the nuclear envelope.     

Heat shock and proinflammatory stressors induce differential localization of heat shock proteins in human monocytes

Heat shock (HS) proteins (HSP) are a family of molecular chaperones induced by environmental stresses such as oxidative injury, and contribute to protection from and adaptation to cellular stress. We investigated in human monocytes the expression and subcellular distribution of hsp70 and hsc70 after HS and inflammation-related stresses leading to generation of reactive oxygen species by these cells, such as the phorbol ester PMA and erythrophagocytosis (E phi). By combining immunofluorescent staining and Western blot on subcellular fractions, we found that all three stress factors resulted in an increased hsp70 expression, however the subcellular distribution pattern was different depending on the type of stress. While HS induced a rapid translocation of hsp70 into the nucleus, no nuclear translocation of hsp70 was observed after PMA or E phi. Neither of the examined stresses induced membrane expression of hsp70. The observed differences in subcellular distribution pattern might relate to distinct regulation and specific functions of hsp70 in inflammation.     

Heat shock proteins and heat adaptation of the whole organism

Adaptation to heat may occur through acclimatization or thermotolerance; however, the linkage of these phenomena is poorly understood. The importance of heat shock proteins (HSPs) in thermotolerance and differences in their accumulation in organisms adapted to the heat suggest a role for HSPs in acclimatization as well. The role of HSPs in heat adaptation of the whole organism and the interrelationships among heat adaptation, endotoxin tolerance, and cytokine resistance through HSPs are reviewed.     

Heat conditioning induces heat shock proteins in broiler chickens and turkey poults

Peripheral leukocyte heat shock proteins (HSP: HSP90, HSP70, and HSP23) from broiler chickens and turkey poults were induced by in vitro and in vivo high temperature exposure. Heat conditioning, via a daily 1 h exposure to 41 C, enhanced in vitro HSP expression in leukocytes from chickens heat-conditioned for 1 to 2 wk, and a similar response was found in turkey poults with 3 wk of heat conditioning causing the greatest HSP expression. In vivo heat exposure trials caused maximization of HSP expression after 1 wk of daily heat conditioning exposures in broilers, but no additional enhancement was seen in chickens heat conditioned for 2 wk. Enhancement in HSP expression was evident for periods up to 4 wk after termination of the daily heat conditioning episodes.     

GTP-binding proteins in plants: new members of an old family

Regulatory guanine nucleotide-binding proteins (G proteins) have been studied extensively in animal and microbial organisms, and they are divided into the heterotrimeric and the small (monomeric) classes. Heterotrimeric G proteins are known to mediate signal responses in a variety of pathways in animals and simple eukaryotes, while small G proteins perform diverse functions including signal transduction, secretion, and regulation of cytoskeleton. In recent years, biochemical analyses have produced a large amount of information on the presence and possible functions of G proteins in plants. Further, molecular cloning has clearly demonstrated that plants have both heterotrimeric and small G proteins. Although the functions of the plant heterotrimeric G proteins are yet to be determined, expression analysis of an Arabidopsis G alpha protein suggests that it may be involved in the regulation of cell division and differentiation. In contrast to the very few genes cloned thus far that encode heterotrimeric G proteins in plants, a large number of small G proteins have been identified by molecular cloning from various plants. In addition, several plant small G proteins have been shown to be functional homologues of their counterparts in animals and yeasts. Future studies using a number of approaches are likely to yield insights into the role plant G proteins play.     

Becoming an adaptive new professional: Going beyond Plante's principles.

Expounds upon T. G. Plante's (see record 1998-12169-017 and 1996-00441-014) strategies for success in searching for postdoctoral career opportunities. The current authors extend Plante's work by offering 10 principles to help doctoral aspirants and new professionals adapt to the current health care system and develop rewarding roles in professional psychology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gap junction channels: new roles in disease

The importance of intercellular communication to complex cellular processes such as development, differentiation, growth, propagation of electrical impulses and diffusional feeding has long been appreciated. The realization that intercellular communication is mediated by gap junction channels, which are in turn comprised of a diverse family of proteins called the connexins, has provided new tools and avenues for studying the role of intercellular communication in these important cellular processes. The identification of different connexin isoforms has not only enabled the development of specific reagents to study connexin expression patterns, but has also allowed the functional properties of the different connexin isoforms and how they interact with each other, to be explored. Increasingly, the knowledge gained from studying connexin diversity is being used to investigate the role played by gap junction channels in a number of diseases. In this article we highlight selected cases where gap junction channels have been shown or are believed to be directly involved in the disease process.     

Memorability functions as an indicator of qualitative age differences in text recall.

An analysis in which the probability of text unit recall for older adults [p(Re|O)] is plotted as a function of this probability for the young [p(Re|Y)] is considered as one way to assess whether there are qualitative differences in text recall for young and old. The application of this relative memorability analysis to previously reported data dealing with the immediate recall of spoken sentences (Stine, Wingfield, & Poon, 1986) revealed that although older adults show qualitative recall similar to younger adults when informational density is low, they show less discrimination among text elements when informational density is increased. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heat shock in human neutrophils: superoxide generation is inhibited by a mechanism distinct from heat-denaturation of NADPH oxidase and is protected by heat shock proteins in thermotolerant cells

Through binding to cholecystokinin (CCK) A receptors, CCK is an important physiologic regulator of both gallbladder contraction and pancreatic enzyme secretion. In this work, we have used a combination of hybridization screening of a cDNA library and polymerase chain reaction to clone a 2.1 kb cDNA which encodes the human gallbladder CCKA receptor. Nucleotide sequence analysis revealed an open reading frame encoding a 428 amino acid protein, with seven putative transmembrane domains and a high degree of homology with the rat CCKA receptor. COS cells transfected with this cDNA clone bound CCK-8 and L-364,718 with high affinities appropriate for the CCKA receptor, and exhibited a transient increase in intracellular calcium in response to CCK. This should provide an important resource for the analysis of the role of this receptor in human physiology and pathophysiology.     

Mammalian protein RAP46: an interaction partner and modulator of 70 kDa heat shock proteins

A ubiquitously expressed nuclear receptor-associating protein of approximately 46 kDa (RAP46) was identified recently. Interaction experiments with in vitro-translated proteins and proteins contained in cell extracts revealed that a great variety of cellular regulators associate with RAP46. However, in direct interaction tests by the far-Western technique, only 70 kDa proteins showed up and were identified as members of the 70 kDa heat shock protein (hsp70) family. Interaction is specific since not all members of the hsp70 family bind to RAP46; interaction occurs through their ATP-binding domain. RAP46 forms complexes with hsp70 in mammalian cells and interacts with hsp70 in the yeast two-hybrid system. Consistent with the fact that hsp70 can bind a multitude of proteins, we identified heteromeric complexes of RAP46-hsp70 with some selected proteins, most notably c-Jun. Complex formation is increased significantly by pre-treatment with alkaline phosphatase, thus suggesting modulation of interactions by protein phosphorylation. We observed that RAP46 interferes with efficient refolding of thermally denatured luciferase. Moreover, ATP-dependent binding of misfolded proteins to hsp70 was greatly inhibited by RAP46. These data suggest that RAP46 functions as a regulator of hsp70 in higher eukaryotes.     

Building team adaptive capacity: The roles of sensegiving and team composition.

The current study draws on motivated information processing in groups theory to propose that leadership functions and composition characteristics provide teams with the epistemic and social motivation needed for collective information processing and strategy adaptation. Three-person teams performed a city management decision-making simulation (N=74 teams; 222 individuals). Teams first managed a simulated city that was newly formed and required growth strategies and were then abruptly switched to a second simulated city that was established and required revitalization strategies. Consistent with hypotheses, external sensegiving and team composition enabled distinct aspects of collective information processing. Sensegiving prompted the emergence of team strategy mental models (i.e., cognitive information processing); psychological collectivism facilitated information sharing (i.e., behavioral information processing); and cognitive ability provided the capacity for both the cognitive and behavioral aspects of collective information processing. In turn, team mental models and information sharing enabled reactive strategy adaptation. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Clinical and counseling psychology: A study of roles and functions.

Defines similarities and differences between clinical and counseling psychology in terms of the relevance of 50 professional activities for these specialties. Perceptions of professional roles and of each other's professional roles were examined in a survey of 84 clinical psychologist academicians, 64 counseling psychologist academicians, 248 clinical psychologist intern supervisors, and 50 counseling psychologist intern supervisors. Ss responded on a 7-point rating scale about the relevance of each of 50 professional activities for defining the professional roles of the 2 specialties. Some clear differences as well as some areas of overlap between the 2 specialties emerged. Most of the differences between them concerned activities associated with one or the other extreme of the normality–pathology continuum. Areas of overlap between the 2 specialties concerned professional activities associated with the middle range of that continuum. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heat shock gene expression during recovery after transient cold shock in Drosophila auraria (Diptera: Drosophilidae)

Newly synthesized polypeptides during recovery from prolonged cold treatment (0 degree to -1 degree C) of Drosophila auraria, a montium subgroup species, of the melanogaster species group, were analysed in denaturing polyacrylamide gels. In addition, during the cold shock recovery period, Northern analysis of the hsp83 mRNA was performed. A significant induction of two polypeptides, which exhibited electrophoretic mobilities, with the heat inducible 83 and 70 kD hsp83 and hsp70 was detected, but no such induction was evident in the so-called 'small' hsp genes. These results are compared and discussed with those observed in D. melanogaster.     

Structural roles of the spore coat proteins in Dictyostelium discoideum

The integrity of spores formed by mutant strains of Dictyostelium discoideum lacking the major spore coat proteins, SP96, SP70, or SP60, was compared to that of wild-type strains. Single, double, and triple knock-out strains developed normally and produced spores which were indistinguishable from wild-type spores by light or electron microscopy. However, the mutant strains were susceptable to staining with the lectin, ricin A, which recognizes a galactose-rich polysaccharide that is normally hidden by overlying spore coat proteins. The intensity of staining with fluorescently labeled ricinA increased as the spore coat proteins were incrementally lost. While these results indicate that the major outer spore coat proteins are not essential for the construction of a multi-layered spore coat in Dictyostelium, they show that the spores are more porous which might make them at risk to predators before germination.     

Role of heat shock proteins in heart transplant rejection

STUDY OBJECTIVE: To study secular trends of placental abruption (PA), the effects of demographic variables and the use of cesarean section (CS) associated with PA. DESIGN: A population based cohort study. SETTING: The Medical Birth Registry of Norway. PATIENTS: 9,592 cases of PA of a total of 1,446,154 births notified, i.e. all births in Norway 1967-1991. MAIN RESULTS: The PA proportion was 6.6 per 1000 births of a gestational age of 16 weeks or more, ranging from 5.3 in 1971 to 9.1 in 1990. Birth order two had the lowest proportion and it increased by maternal age. The PA proportion decreased by gestational age from 86.4 per 1000 below 28 weeks to 3.4 in term pregnancies. The PA proportion per 10,000 pregnancies at risk increased from 1.3 in the 28th week to 14.1 in the 42nd week. A secular trend of a decreasing but still high relative risk of PA in SGA-births at any gestational age increased from 1967 through 1991. The relative risk of PA of Apgar score <7 after five minutes, adjusted for gestational age, was 7.8. CONCLUSIONS: Inspite of an increasing CS rate, an increasing proportion of PA was noted from 1967 through 1991. The proportion was lowest for birth order two and increased by maternal age. To an increasing extent, PA births were centralized. SGA, prematurity and asphyxia were major problems associated with PA. A tendency towards larger infants and a decreasing relative risk of PA in SGA-births might be attributable to improvements in antenatal care.     

Heat shock treatment decreases the mortality of sepsis in rats

Sepsis is an increasingly common and lethal diagnosis in hospitalized patients. In spite of the advances in antibiotics and medical equipment, the mortality rate has not been improved in the last decade. Recently, heat shock proteins (Hsps) have been well documented to play a self-protective role in almost all living cells under various pathological and physiological stresses through a mechanism known as thermotolerance or cross tolerance. The present study was designed to investigate the expression of Hsp72 and the protective role of pre-induction of Hsps in the mortality during different phases of sepsis. Adult male Sprague-Dawley rats were employed in the study. Sepsis was induced by cecal ligation and puncture (CLP). Heat shock treatment was performed 16 hrs before sepsis induction by heating the rats whole-bodily with an electric heating pad under general anesthesia. The mortality rates with time in both control and preheated groups were monitored. Hsp72 was detected by SDS-PAGE, Western blotting and immunostaining in the brain, heart, liver, kidney, lung, adrenal gland, muscle and lymphocytes. The results show that both early (9 hrs post-CLP) and late (18 hrs post-CLP) sepsis failed to increase the synthesis of Hsp72. Previous induction of Hsps by heat shock treatment significantly decreased the mortality rate of late sepsis. Applying a sufficient inducer to lymphocytes of late sepsis reversed the synthesis of Hsp72 from inactive state into an over-expressive situation in vitro. These results suggest that Hsps are involved in the pathogenesis of sepsis and the involvement of Hsps during the progression of sepsis could add to a first line of host defense against invasive pathogens. Searching for an acceptable agent or less invasive method that leads to increased Hsps expression may provide a means for better treatment of severe infection.