Pre-inhalation of hydrogen-rich gases protect against caerulein-induced mouse acute pancreatitis while enhance the pancreatic Hsp60 protein expression

Background Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. Aim of this study was to investigate effect of hydrogen pretreatment on AP and the mechanisms, focusing on pancreatic oxidative stress and Hsp60 expression. Methods 80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1 h, 3 h and 5 h (n = 6–8). Mouse AP model was induced by intraperitoneal injection of 50 μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance. Results The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1 h and 5 h. Conclusions Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

Pre-inhalation of hydrogen-rich gases protect against caerulein-induced mouse acute pancreatitis while enhance the pancreatic Hsp60 protein expression

Background: Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. Aim of this study was to investigate effect of hydrogen pretreatment on AP and the mechanisms, focusing on pancreatic oxidative stress and Hsp60.Methods: 80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1h, 3h and 5h (n=6- 8). Mouse AP model was induced by intraperitoneal injection of 50μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance.Results: The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1h and 5h. Conclusions: Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

Pre-inhalation of Hydrogen-rich Gases Protect Against Caerulein-induced Mouse Acute Pancreatitis While Enhance the Pancreatic Hsp60 Protein Expression

Background: Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. The aim of this study was to investigate effect of hydrogen pretreatment on experimental AP mice, as well as the possible mechanisms, focusing on antioxidant and Hsp60 expression alteration mechanisms.Methods: 80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1h, 3h and 5h (n=6- 8). Mouse AP model was induced by intraperitoneal injection of 50μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance.Results: The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1h and 5h. Conclusions: Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

Differential scanning fluorimetry (DSF) screen to identify inhibitors of Hsp60 protein–protein interactions

Homo-oligomers are difficult drug targets. Here, Differential Scanning Fluorimetry (DSF) is introduced as a method to identify inhibitors of these systems, by discriminating between oligomers and monomers based on their thermal stability.

Protein moonlighting: what is it, and why is it important?

Members of the GroEL/HSP60 protein family have been studied for many years because of their critical roles as ATP-dependent molecular chaperones, so it might come as a surprise that some have important functions in ATP-poor conditions, for example, when secreted outside the cell. At least some members of each of the HSP10, HSP70, HSP90, HSP100 and HSP110 heat shock protein families are also ‘moonlighting proteins’. Moonlighting proteins exhibit more than one physiologically relevant biochemical or biophysical function within one polypeptide chain. In this class of multifunctional proteins, the multiple functions are not due to gene fusions or multiple proteolytic fragments. Several hundred moonlighting proteins have been identified, and they include a diverse set of proteins with a large variety of functions. Some participate in multiple biochemical processes by using an active site pocket for catalysis and a different part of the protein's surface to interact with other proteins. Moonlighting proteins play a central role in many diseases, and the development of novel treatments would be aided by more information addressing current questions, for example, how some are targeted to multiple cellular locations and how a single function can be targeted by therapeutics without targeting a function not involved in disease. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

HSP60 Predicts Survival in Advanced Serous Ovarian Cancer

ObjectiveHeat shock protein 60 (HSP60) plays an essential role in malignant cell survival. We evaluated the prognostic and treatment predictive value of HSP60 in advanced ovarian cancer.MethodsFresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 fulfilled the eligibility criteria, that is, International Federation of Gynecology and Obstetrics stage IIC-IV, serous/endometrioid tumors, platinum-based chemotherapy, and specimens with 50% tumor cells or greater. Heat shock protein 60 mRNA and protein expression was determined by real-time polymerase chain reaction and immunohistochemistry. We estimated the association between HSP60 and overall survival (OS) and platinum-free interval (PFI) by Cox proportional hazards models and its relationship with treatment response by Fisher’s exact test. Median follow-up was 60 months.ResultsHigh HSP60 mRNA expression was associated with shorter OS (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.3–8.5) and PFI (HR, 3.3; 95% CI, 1.5–7.2). Likewise, high HSP60 protein expression was associated with shorter OS (HR, 3.2; 95% CI, 1.5–7.1) and PFI (HR, 2.6; 95% CI, 1.3–5.3). Median survival for patients with high HSP60 protein expression was 31 months compared with 55 months for low expression cases (P = 0.016). The impact on OS and PFI was even stronger in the subgroup of grade 3 serous tumors. All patients with low HSP60 levels responded to first-line chemotherapy.ConclusionHeat shock protein 60 may identify groups of advanced serous ovarian cancer with different prognosis and treatment response.