Unraveling the Connection: Pain and Endoplasmic Reticulum Stress.

Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding and calcium dynamics.

Changes in breathing pattern during severe hypothermia and autoresuscitation from hypothermic respiratory arrest in anesthetized mice.

Some evidence suggests that both hypothermia and anesthesia can exert similar effects on metabolism and ventilation. This study examined the synergistic effects of anesthesia and hypothermia on ventilation in spontaneously breathing adult mice under three different conditions, that is, (1) pentobarbital group (n = 7) in which mice were anesthetized with intraperitoneal pentobarbital of 80 mg/kg, (2) sevoflurane-continued group (n = 7) in which mice were anesthetized with 1 MAC sevoflurane, and (3) sevoflurane-discontinued group (n = 7) in which sevoflurane was discontinued at a body temperature below 22˚C. We cooled mice in each group until breathing ceased and followed this with artificial rewarming while measuring changes in respiratory variables and heart rate.

Pharmacological Chaperones Attenuate the Development of Opioid Tolerance.

Opioids are potent analgesics widely used to control acute and chronic pain, but long-term use induces tolerance that reduces their effectiveness. Opioids such as morphine bind to mu opioid receptors (MORs), and several downstream signaling pathways are capable of inducing tolerance. We previously reported that signaling from the endoplasmic reticulum (ER) contributed to the development of morphine tolerance.

A high concentration of sevoflurane induces gasping breaths in mice.

The purpose of this study is to compare changes in breathing patterns elicited by hypoxic stress and/or anesthetic stress in mice. Spontaneously breathing anesthetized mice whose tracheae were intubated with a tracheal cannula were challenged with hypoxic stress and/or sevoflurane-induced anesthetic stress while ventilation was measured with a pneumotachograph. When anesthesia was maintained at a light level with inhalation of 2.

Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response.

Preclinical studies have shown that exposure of the developing brain to inhalational anesthetics can cause neurotoxicity. However, other studies have claimed that anesthetics can exert neuroprotective effects. We investigated the mechanisms associated with the neurotoxic and neuroprotective effects exerted by inhalational anesthetics.

Pathogenic Effects of Impaired Retrieval between the Endoplasmic Reticulum and Golgi Complex.

Cellular activities, such as growth and secretion, are dependent on correct protein folding and intracellular protein transport. Injury, like ischemia, malnutrition, and invasion of toxic substances, affect the folding environment in the endoplasmic reticulum (ER). The ER senses this information, following which cells adapt their response to varied situations through the unfolded protein response.

A simple and safe method for tracheal intubation using a supraglottic intubation-aid device in mice.

Although mice are a commonly used animal species in experimental medicine, airway management of this species is not easy due to their small size. In order to develop a new method of tracheal intubation in mice, we produced a supraglottic intubation-aid conduit (SIAC) for mice, and tested the efficacy of this device in spontaneously breathing mice anesthetized with sevoflurane inhalation. The success rate of tracheal intubation with the crude prototype of the SIAC was 50% and adverse effects on respiration and some trauma in the upper airway were occasionally observed.

Decreased Protein Quality Control Promotes the Cognitive Dysfunction Associated With Aging and Environmental Insults.

Most neurodegenerative diseases are sporadic and develop with age. Degenerative neural tissues often contain intra- and extracellular protein aggregates, suggesting that the proteostasis network that combats protein misfolding could be dysfunctional in the setting of neurodegenerative disease. Binding immunoglobulin protein (BiP) is an endoplasmic reticulum (ER) chaperone that is crucial for protein folding and modulating the adaptive response in early secretory pathways.

The Role of BiP Retrieval by the KDEL Receptor in the Early Secretory Pathway and its Effect on Protein Quality Control and Neurodegeneration.

Protein quality control in the early secretory pathway is a ubiquitous eukaryotic mechanism for adaptation to endoplasmic reticulum (ER) stress. An ER molecular chaperone, immunoglobulin heavy chain-binding protein (BiP), is one of the essential components in this process. BiP interacts with nascent proteins to facilitate their folding.

Sublethal endoplasmic reticulum stress caused by the mutation of immunoglobulin heavy chain-binding protein induces the synthesis of a mitochondrial protein, pyrroline-5-carboxylate reductase 1.

Most human neurodegenerative diseases are sporadic and appear later in life. Aging and neurodegeneration are closely associated, and recent investigations reveal that endoplasmic reticulum (ER) stress is involved in the progression of these features. Immunoglobulin heavy chain-binding protein (BiP) is an ER chaperone that is central to ER functions.

Late-onset of spinal neurodegeneration in knock-in mice expressing a mutant BiP.

Most human neurodegenerative diseases are sporadic, and appear later in life. While the underlying mechanisms of the progression of those diseases are still unclear, investigations into the familial forms of comparable diseases suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis. Binding immunoglobulin protein (BiP) is an ER chaperone that is central to ER function.

The effect of endoplasmic reticulum stress on neurotoxicity caused by inhaled anesthetics.

Background: The mechanisms by which inhaled anesthetics cause neurotoxicity are not well clarified. Exposure to inhaled anesthetics induces a release of Ca from the endoplasmic reticulum (ER) into the cytosol. Aberrant Ca mobilization may alter the protein-folding environment in the ER, causing ER stress.

Valproate attenuates the development of morphine antinociceptive tolerance.

Morphine is a potent opioid analgesic. Repeated administration of morphine induces tolerance, thus reducing the effectiveness of analgesic treatment. Although some adjuvant analgesics can increase morphine analgesia, the precise molecular mechanism behind their effects remains unclear.

BiP, an endoplasmic reticulum chaperone, modulates the development of morphine antinociceptive tolerance.

Morphine is a potent analgesic, but the molecular mechanism for tolerance formation after repeated use is not fully understood. Binding immunoglobulin protein (BiP) is an endoplasmic reticulum (ER) chaperone that is central to ER function. We examined knock-in mice expressing a mutant BiP with the retrieval sequence deleted in order to elucidate physiological processes that are sensitive to BiP functions.

Dysfunction of the ER chaperone BiP accelerates the renal tubular injury.

Tubular-interstitial injury plays a key role in the progression of chronic kidney disease. Although endoplasmic reticulum (ER) stress plays significant roles in the development of chronic diseases such as neurodegenerative disease, cardiomyopathy and diabetes mellitus, its pathophysiological role in chronic renal tubular cell injury remains unknown. BiP is an essential chaperone molecule that helps with proper protein folding in the ER.

Altered quality control in the endoplasmic reticulum causes cortical dysplasia in knock-in mice expressing a mutant BiP.

Binding immunoglobulin protein (BiP) is an endoplasmic reticulum (ER) molecular chaperone that is central to ER function. We examined knock-in mice expressing a mutant BiP in order to elucidate physiological processes that are sensitive to BiP functions during development and adulthood. The mutant BiP lacked the retrieval sequence that normally functions to return BiP to the ER from the secretory pathway.

Differential binding properties of B7-H1 and B7-DC to programmed death-1.

Programmed death-1 (PD-1) is a negative regulatory receptor expressed on activated T and B cells. Two ligands for PD-1, B7-H1 (PD-L1) and B7-DC (PD-L2), have been identified, but their binding properties have not been characterized yet. In this study, we generated soluble Ig fusion proteins of these molecules and examined the kinetics and relative affinities of the interactions between B7-H1 or B7-DC and PD-1 by flow cytometry and surface plasmon resonance.