Search

Growth hormone-releasing hormone antagonists (GHRHAnt) have been associated with antitumor and antioxidative activities. The present study investigates for the first time the effects of those compounds towards pro-inflammatory cytokine expression in a murine model of cecal ligation and puncture (CLP) - induced sepsis. The results indicate that GHRHAnt JV-1-36 significantly suppressed IL-1α, IL-6, and pSTAT3 activation in septic lungs. Moreover, GHRHAnt treatment reduced bronchoalveolar lavage fluid (BALF) protein concentration, suggesting a protective effect of that compound in sepsis-induced lung edema. Based on those findings, it is suggested that GHRHAnt may represent an exciting new therapeutic possibility in sepsis-induced endotoxemia and lung injury., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The unfolded protein response (UPR) is a highly conserved molecular machinery, which protects the cells against a diverse variety of stimuli. Activation of this element has been associated with both human health and disease. The purpose of the current manuscript is to provide the most updated information on the involvement of UPR towards the improvement; or deterioration of cardiovascular functions. Since UPR is consisted of three distinct elements, namely the activating transcription factor 6, the protein kinase RNA-like endoplasmic reticulum kinase; and the inositol-requiring enzyme-1α, a highly orchestrated manipulation of those molecular branches may provide new therapeutic possibilities against the severe outcomes of cardiovascular disease., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The unfolded protein response element protects against endoplasmic reticulum stress and delivers protection towards potentially harmful challenges. The components of this multi-branch molecular machinery, namely the protein kinase RNA-like ER kinase, the activating transcription factor 6, and the inositol-requiring enzyme-1α; expand the endoplasmic reticulum capacity to support cellular function under stress conditions. In the present study, we employed bovine pulmonary aortic endothelial cells and mice to investigate the possibility that the Hsp90 inhibitors Tanespimycin (17-AAG) and Luminespib (AUY-922) exert the capacity to trigger the unfolded protein response. The induction of the unfolded protein response regulators immunoglobulin heavy-chain-binding protein, endoplasmic reticulum oxidoreductin-1alpha; and protein disulfide isomerase was also examined. It appears that both inhibitors capacitate the induction of the unfolded protein response element in vitro, since lung cells exposed to 1, 2 and 10 μM of 17-AAG or AUY-922 for 4, 6, 8, 16 and 48 h demonstrated increased levels of those proteins. Similar events occurred in the lungs of mice treated with AUY-922. Thus, our study demonstrates that Hsp90 inhibition triggers the activities of the unfolded protein response, and suggests that this molecular machinery contributes in the protective action of Hsp90 inhibitors in the lung microvasculature., (Copyright © 2019 Elsevier Inc. All rights reserved.)