Publications (2)3.56 Total impact
- [show abstract] [hide abstract]
ABSTRACT: The present study aimed to determine whether restraint stress aggravates kidney injury caused by a crush injury through endoplasmic reticulum stress (ERS). In this study, Sprague-Dawley rat restraint stress, crush injury, and stressful injury models consisting of restraint stress and crush injury were established. An ERS inhibitor, Salubrinal (Sal), was administered intraperitoneally 30 minutes before induction of daily injury in the stressful injury group. At the end of the experimental procedures, plasma levels of noradrenaline and adrenaline, creatine phosphokinase, creatinine, and blood urea nitrogen were measured. Kidneys were harvested, and paraffin-embedded sections of kidney tissues were processed for hematoxylin-eosin staining and TUNEL assay to verify pathologic changes. Western blot was used to determine the protein levels of glucose-regulated protein 78, CCAAT/enhancer-binding protein-homologous protein, caspase 12, caspase 3, and MCP-1 in kidney specimens. Compared with crush injury, the most significant changes in kidney injury occurred in the stressful injury group, which was inhibited by Sal. The results suggested that restraint stress aggravates kidney injury caused by a crush injury, and the mechanism might involve ERS. Further study showed that double attacks induced a significant increase in the levels of glucose-regulated protein 78, CCAAT/enhancer-binding protein-homologous protein, caspase 12, and caspase 3, which was inhibited by Sal. The same changes were observed using the TUNEL assay. Double attacks also induced an increased expression of the proinflammatory cytokine, MCP-1, which was inhibited by Sal. Apoptosis and inflammation induced by ERS are important mechanisms by which restraint stress aggravates kidney injury caused by a crush injury.The journal of trauma and acute care surgery. 10/2013; 75(5):798-806.
- [show abstract] [hide abstract]
ABSTRACT: The hypothalamic-pituitary-adrenal (HPA) axis is critical to mediating the body's response to stress. Corticotropin releasing hormone (CRH) plays a central role in controlling the stress response and regulating the HPA axis. Recent findings support CRH participates in the stress-induced hippocampal neuron apoptosis, but the underlying mechanisms are not fully understood. Our present study demonstrates that CRH can independently decrease hippocampal neuron cell viability in vitro in a concentration- and time-dependent manner. CRH receptor 1 (CRHR1) is involved in CRH-induced neuron apoptosis. Endoplasmic reticulum (ER) stress response marker, glucose-regulated protein 78 (GRP78), either protein or mRNA, is significantly elevated after treatment of CRH, and decreased when co-treated with salubrinal, ER stress inhibitor. The ER stress associated proapoptotic transcription factor C/EBP homologous protein (CHOP) and cleavage of caspase-12 protein expression are also increased following CRH treatment. Furthermore, we investigate which ER stress cascades are affected by CRH. CRH activates inositol-requiring enzyme 1 (IRE1), apoptosis signal regulating kinase 1 (ASK1), and c-jun kinase (JNK). Neuron apoptotic rate, examined by flow cytometry, is increased when CRH treatment and attenuated by salubrinal, thioredoxin (ASK1 inhibitor) and SP600125 (JNK inhibitor). Therefore, current data indicate that ER stress, through activating the IRE1/ASK1/JNK cascade, plays an important role in CRH-induced neuron apoptosis.Experimental Cell Research 04/2012; 318(6):732-40. · 3.56 Impact Factor