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Acute lung injury and endoplasmic reticulum stress

Yonghong Lei, Xue Li, Fang Yuan, Lu Liu, Juan Zhang, Yanping Yang, Jieqiong Zhao, Yan Han, Jun Ren, Xiaobing Fu
Paraquat is a nitrogen herbicide imposing severe organ toxicity in human leading to acute lung injury and heart failure. The present study was designed to examine the impact of ablation of the innate proinflammatory mediator toll-like receptor 4 (TLR4) in paraquat-induced cardiac contractile dysfunction and the underlying mechanisms involved with a focus on endoplasmic reticulum (ER) stress and apoptosis. Adult male wild-type (WT) and TLR4 knockout (TLR4(-/-) ) mice were challenged with paraquat (45 mg/kg, i...
July 21, 2016: Environmental Toxicology
Jutaro Fukumoto, Ruan Cox, Itsuko Fukumoto, Young Cho, Prasanna Tamarapu Parthasarathy, Lakshmi Galam, Richard F Lockey, Narasaiah Kolliputi
Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase kinase (MAP3K) family, is activated by various stimuli, which include oxidative stress, endoplasmic reticulum (ER) stress, calcium influx, DNA damage-inducing agents and receptor-mediated signaling through tumor necrosis factor receptor (TNFR). Inspiration of a high concentration of oxygen is a palliative therapy which counteracts hypoxemia caused by acute lung injury (ALI)-induced pulmonary edema. However, animal experiments so far have shown that hyperoxia itself could exacerbate ALI through reactive oxygen species (ROS)...
2016: PloS One
Tess V Dupre, Mark A Doll, Parag P Shah, Cierra N Sharp, Alex Kiefer, Michael T Scherzer, Kumar Saurabh, Doug Saforo, Deanna Siow, Lavona Casson, Gavin E Arteel, Alfred Bennett Jenson, Judit Megyesi, Rick G Schnellmann, Levi J Beverly, Leah J Siskind
Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury...
February 1, 2016: American Journal of Physiology. Renal Physiology
H-G Moon, Y Cao, J Yang, J H Lee, H S Choi, Y Jin
Despite decades of research, the pathogenesis of acute respiratory distress syndrome (ARDS) remains poorly understood, thus impeding the development of effective treatment. Diffuse alveolar damage (DAD) and lung epithelial cell death are prominent features of ARDS. Lung epithelial cells are the first line of defense after inhaled stimuli, such as in the case of hyperoxia. We hypothesized that lung epithelial cells release 'messenger' or signaling molecules to adjacent or distant macrophages, thereby initiating or propagating inflammatory responses after noxious insult...
December 10, 2015: Cell Death & Disease
Kent S Tadokoro, Ujala Rana, Xigang Jing, G Ganesh Konduri, Qing R Miao, Ru-Jeng Teng
Nogo-B and its receptor (NgBR) are involved in blood vessel growth in developing lungs, but their role in pulmonary artery smooth muscle cell (PASMC) growth is unknown. We hypothesized that NgBR regulates growth of PASMCs by modulating the function of endoplasmic reticulum (ER) and formation of reactive oxygen species (ROS). In utero constriction of the ductus arteriosus created pulmonary hypertension in fetal lambs (hypertensive fetal lamb [HTFL]). PASMCs isolated 8 days after surgery were assessed for the alteration of protein levels by immunoblots and ROS formation by dihydroethidium and Cell ROX deep red fluorescence...
June 2016: American Journal of Respiratory Cell and Molecular Biology
Rong Hu, Zhi-Feng Chen, Jia Yan, Qi-Fang Li, Yan Huang, Hui Xu, Xiao-Ping Zhang, Hong Jiang
Diverse clinical factors, including intestinal ischemia, contribute to acute lung injury (ALI), which has up to a 40% mortality rate. During the development of lung injury an immune response is elicited that exacerbates the lung insult. Neutrophils have been well studied in mediating the pulmonary insults through an assortment of mechanisms, such as release of granule contents and production of proinflammatory cytokines due to the overactivation of complement and cytokines. In this study, we found that enhanced endoplasmic reticulum (ER) stress was observed in infiltrated neutrophils in the early stage of an ALI mice model...
November 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Cheng-Lung Chen, Jiunn-Wang Liao, Oliver Yoa-Pu Hu, Li-Heng Pao
Tubular cell apoptosis significantly contributes to cisplatin-induced acute kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium channel, participates in apoptosis, its involvement in cisplatin-induced AKI is unknown. Here, we found that cisplatin treatment triggered an early induction of KCa3.1 expression associated with HK-2 cell apoptosis, the development of renal tubular damage, and apoptosis in mice. Treatment with the highly selective KCa3.1 blocker TRAM-34 suppressed cisplatin-induced HK-2 cell apoptosis...
September 2016: Archives of Toxicology
Shaoying Li, Liang Guo, Pin Qian, Yunfeng Zhao, Ao Liu, Fuyun Ji, Liutong Chen, Xueling Wu, Guisheng Qian
BACKGROUND: Alveolar epithelial cell death plays a critical role in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. Increased autophagy has a dual effect on cell survival. However, it is not known whether autophagy promotes death or survival in human alveolar epithelial cells exposed to LPS. METHODS: Genetic and pharmacological approaches were used to evaluate the effect of autophagy on A549 cell viability upon LPS exposure. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways were examined with immunoblotting studies to further explore underlying mechanisms...
2015: Cellular Physiology and Biochemistry
Hai-Feng Li, Shi-Xing Zhao, Bao-Peng Xing, Ming-Li Sun
Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline...
March 2015: Neural Regeneration Research
Chhinder P Sodhi, Hongpeng Jia, Yukihiro Yamaguchi, Peng Lu, Misty Good, Charlotte Egan, John Ozolek, Xiaorong Zhu, Timothy R Billiar, David J Hackam
The mechanisms that lead to the development of remote lung injury after trauma remain unknown, although a central role for the gut in the induction of lung injury has been postulated. We hypothesized that the development of remote lung injury after trauma/hemorrhagic shock requires activation of TLR4 in the intestinal epithelium, and we sought to determine the mechanisms involved. We show that trauma/hemorrhagic shock caused lung injury in wild-type mice, but not in mice that lack TLR4 in the intestinal epithelium, confirming the importance of intestinal TLR4 activation in the process...
May 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Zhi-Wei Liu, Hai-Ying Wang, Lan Guan, Bin Zhao
BACKGROUND: The present study was undertaken to examine the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress in alveolar epithelial cells of rats with acute lung injury (ALI) induced by oleic acid (OA). METHODS: Seventy-two male Sprague Dawley (SD) rats were divided into control group, oleic acid-induced ALI group (OA group), oleic acid-induced ALI with sodium hydrosulfide (NaHS) pretreatment group (OA+NaHS group), and sodium hydrosulfide treatment group (NaHS group)...
2015: World Journal of Emergency Medicine
Zhu Xiaoji, Meng Xiao, Xu Rui, Chu Haibo, Zhao Chao, Lian Chengjin, Wang Tao, Guo Wenjun, Zhang Shengming
Sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation...
December 23, 2014: Toxicology and Industrial Health
Xiaomiao Zhang, Fengying Gao, Qian Li, Zhixia Dong, Bo Sun, Lili Hou, Zhuozhe Li, Zhenwei Liu
PURPOSE: The aim of this study was to evaluate the effect and related mechanisms of Mesenchymal stem cells (MSCs) and Angiotensin converting enzyme II (ACE II) on acute lung injury (ALI). METHODS: MSCs were separated from umbilical cord cells, and the changes of phenotype before and after ACE II silence were observed using Flow Cytometer. ALI model was induced by 10 mg/mL bleomycin in 60 Balb/c mice, and the rest 8 mice were regarded as the baseline group. The mice were randomly divided into four groups (n = 15): control, ACE II, stem, and stem + ACE II...
February 2015: Experimental Lung Research
Antony Leonard, Adrienne W Paton, Monaliza El-Quadi, James C Paton, Fabeha Fazal
Endoplasmic Reticulum (ER) stress, caused by disturbance in ER homeostasis, has been implicated in several pathological conditions such as ischemic injury, neurodegenerative disorders, metabolic diseases and more recently in inflammatory conditions. Our present study aims at understanding the role of ER stress in endothelial cell (EC) inflammation, a critical event in the pathogenesis of acute lung injury (ALI). We found that preconditioning human pulmonary artery endothelial cells (HPAEC) to ER stress either by depleting ER chaperone and signaling regulator BiP using siRNA, or specifically cleaving (inactivating) BiP using subtilase cytotoxin (SubAB), alleviates EC inflammation...
2014: PloS One
Hua Guo, Chao Jiang, Xiaomin Sun
To explore therapeutic effects and underlying mechanism of Salubrinal combined with Ulinastatin (UTI) on acute Paraquat (PQ) poisoning. Four hundred rats were randomly allocated into UTI group, SAL group, SAL + UTI and control group according to random number table with 100 rats in each group. Acute PQ poisoning models were established, and all rats received UTI, Salubrinal, SAL + UTI and normal saline injection, respectively. Afterward, we analyzed the change of lung tissue and explored the mechanism. Acute PQ poisoning caused significantly damage in rat lung tissue structure, and UTI could effectively repair lung tissue damage...
December 2014: Cell Biochemistry and Biophysics
Zhijian Zhang, Yaoyao Dong, Xiaoping Li, Libo Peng
OBJECTIVE: To investigate the effect of total flavonoids from astragalus complanatus (FAC) on attenuating lung injury resulted from paraquat (PQ) poisoning by inhibiting excessive endoplasmic reticulum stress (ERS) and c-Jun N-terminal kinase (JNK) pathway in rat. METHODS: Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups (n=8 in each group), including control group, model group, dimethyl sulfoxide (DMSO) vehicle control group, and FAC in low, medium, and high dosage groups...
June 2014: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Fumihiko Namba, Hayato Go, Jennifer A Murphy, Ping La, Guang Yang, Shaon Sengupta, Amal P Fernando, Mekdes Yohannes, Chhanda Biswas, Suzanne L Wehrli, Phyllis A Dennery
Premature infants exposed to hyperoxia suffer acute and long-term pulmonary consequences. Nevertheless, neonates survive hyperoxia better than adults. The factors contributing to neonatal hyperoxic tolerance are not fully elucidated. In contrast to adults, heme oxygenase (HO)-1, an endoplasmic reticulum (ER)-anchored protein, is abundant in the neonatal lung but is not inducible in response to hyperoxia. The latter may be important, because very high levels of HO-1 overexpression are associated with significant oxygen cytotoxicity in vitro...
2014: PloS One
Lata Kaphalia, William J Calhoun
Chronic alcohol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). A significant amount of ingested alcohol reaches airway passages in the lungs and can be metabolized via oxidative and non-oxidative pathways. About 90% of the ingested alcohol is metabolized via hepatic alcohol dehydrogenase (ADH)-catalyzed oxidative pathway. Alcohol can also be metabolized by cytochrome P450 2E1 (CYP2E1), particularly during chronic alcohol abuse...
October 24, 2013: Toxicology Letters
Te I Weng, Hsiao Yi Wu, Bo Lin Chen, Shing Hwa Liu
Severe acute pancreatitis remains a life-threatening disease with a high mortality rate among a defined proportion of those affected. Apoptosis has been hypothesized to be a beneficial form of cell death in acute pancreatitis. Honokiol, a low-molecular-weight natural product, possesses the ability of anti-inflammation and apoptosis induction. Here, we investigate whether honokiol can ameliorate severe acute pancreatitis and the associated acute lung injury in a mouse model. Mice received six injections of cerulein at 1-h intervals, then given one intraperitoneal injection of bacterial lipopolysaccharide for the induction of severe acute pancreatitis...
May 2012: Shock
Edilson Torres-González, Marta Bueno, Atsuko Tanaka, Laurie T Krug, Dong-Sheng Cheng, Vasiliy V Polosukhin, Dan Sorescu, William E Lawson, Timothy S Blackwell, Mauricio Rojas, Ana L Mora
The incidence of idiopathic pulmonary fibrosis (IPF) increases with age. The mechanisms that underlie the age-dependent risk for IPF are unknown. Based on studies that suggest an association of IPF and γherpesvirus infection, we infected young (2-3 mo) and old (≥18 mo) C57BL/6 mice with the murine γherpesvirus 68. Acute murine γherpesvirus 68 infection in aging mice resulted in severe pneumonitis and fibrosis compared with young animals. Progressive clinical deterioration and lung fibrosis in the late chronic phase of infection was observed exclusively in old mice with diminution of tidal volume...
June 2012: American Journal of Respiratory Cell and Molecular Biology
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