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autophagy ischemia

Qian Sun, Patricia Loughran, Richard Shapiro, Indira H Shrivastava, Daniel J Antoine, Tunliang Li, Zhengzheng Yan, Jie Fan, Timothy R Billiar, Melanie J Scott
: Sterile liver inflammation, such as liver ischemia reperfusion, hemorrhagic shock after trauma and drug-induced liver injury is initiated and regulated by endogenous mediators including DNA and reactive oxygen species. Here we identify a novel mechanism for redox-mediated regulation of AIM2-inflammasome activation in hepatocytes after redox stress in mice, which occurs via interaction with cytosolic HMGB1. We show that in liver during hemorrhagic shock in mice, and in hepatocytes after hypoxia with reoxygenation, cytosolic HMGB1 associates with AIM2 and is required for activation of caspase-1 in response to cytosolic DNA...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ye Li, Yinan Luo, Tianfei Luo, Bin Lu, Chen Wang, Yanhong Zhang, Meihua Piao, Chunsheng Feng, Pengfei Ge
Protein aggregation has been proved to be a pathological basis accounting for neuronal death caused by either transient global ischemia or oxygen glucose deprivation (OGD), and inhibition of protein aggregation is emerging as a potential strategy of preventing brain damage. Trehalose was found to inhibit protein aggregation caused by neurodegenerative diseases via induction of autophagy, whereas its effect is still elusive on ischemia-induced protein aggregation. In this study, we investigated this issue by using rat model of transient global ischemia and SH-SY5Y model of OGD...
October 22, 2016: Molecular Neurobiology
Long-Xing Xue, Zhong-Hang Xu, Jiao-Qi Wang, Cui Yang, Hong-Yu Liu, Wen-Zhao Liang, Qiu-Ye Ji, Jin-Ting He, Yan-Kun Shao, Jing Mang, Zhong-Xin Xu
Activin A (Act A), a member of the transforming growth factor-beta (TGF-β), reduces neuronal apoptosis during cerebral ischemia through Act A/Smads signaling pathway. However, little is known about the effect of Act A/Smads pathway on autophagy in neurons. Here, we found that oxygen-glucose deprivation (OGD)-induced autophagy was suppressed by exogenous Act A in a concentration-dependent manner and enhanced by Act A/Smads pathway inhibitor (ActRIIA-Ab) in neuronal PC12 cells. These results indicate that Act A/Smads pathway negatively regulates autophagy in OGD-treated PC12 cells...
October 18, 2016: Biochemical and Biophysical Research Communications
X F Guo, Y N Zhao, J M Li, C X Chen, S X Li
Objective: To compare the changes in the expression of mTOR and beclin1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion, so as to explore the roles of mTOR/autophagy pathway in global cerebral ischemia/reperfusion injure aggravated by intermittent hypoxia. Methods: One hundred healthy male Wistar rats were randomly divided into: sham operation group(SO group, n=20), intermittent hypoxia group(IH group, n=20), merely ischemia/reperfusion group(I/R group, n=20), intermittent hypoxia ischemia/reperfusion group(IH+ I/R group, n=20), intermittent hypoxia ischemia/reperfusion+ mTOR inhibitor group(Inhibitor group, n=20)...
October 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Qunjun Duan, Weijun Yang, Daming Jiang, Kaiyu Tao, Aiqiang Dong, Haifeng Cheng
Myocardial infarction could result in high morbidity and mortality and heart diseases of children have becoming prevalent. Functions of spermine administration on cardiomyocytes remain unknown. The present study was designed to investigate the role of spermine pretreatment on myocardial ischemia/reperfusion injury (IRI). A cell model of simulated ischemia/reperfusion injury was established by incubating neonatal Sprague-Dawley rat cardiomyocytes in ischemia medium and re-cultured in normal medium. Of note, spermine pretreatment significantly reduced apoptosis and increased viability of immature cardiomyocytes...
2016: American Journal of Translational Research
Yaqian Zhao, Guowei Huang, Shuang Chen, Yun Gou, Zhiping Dong, Xumei Zhang
Folic acid (FA) deficiency is not only associated with an increased risk of ischemic stroke, but also with increased oxidative DNA damage and brain injury after cerebral ischemia-reperfusion. However, the cellular and molecular mechanisms underlying FA deficiency-associated neuropathogenesis are not completely understood. In the present study, we tested the hypothesis that neuronal autophagy in focal cerebral ischemia rats may be involved in the mechanisms of FA deficiency-induced injury to neuronal cells. The results demonstrated that, accompanied by obvious neuron damage, the expression of the autophagic markers LC3 and Beclin-1, and the formation of 8-OHdG (a marker of oxidative stress to DNA) and autophagosomes were significantly increased in the brain cortex after ischemia-reperfusion...
September 7, 2016: Journal of Nutritional Biochemistry
Marzena Ułamek-Kozioł, Ryszard Pluta, Sławomir Januszewski, Janusz Kocki, Anna Bogucka-Kocka, Stanisław J Czuczwar
We review the Alzheimer-related expression of genes following brain ischemia as risk factors for late-onset of sporadic Alzheimer's disease and their role in Alzheimer's disease ischemia-reperfusion pathogenesis. More recent advances in understanding ischemic etiology of Alzheimer's disease have revealed dysregulation of Alzheimer-associated genes including amyloid protein precursor, β-secretase, presenilin 1 and 2, autophagy, mitophagy and apoptosis. We review the relationship between these genes dysregulated by brain ischemia and the cellular and neuropathological characteristics of Alzheimer's disease...
September 5, 2016: Pharmacological Reports: PR
Adam Kassan, Uyen Pham, Quynhmy Nguyen, Melissa E Reichelt, Eunbyul Cho, Piyush M Patel, David M Roth, Brian P Head, Hemal H Patel
Autophagy is a dynamic recycling process responsible for the breakdown of misfolded proteins and damaged organelles, providing nutrients and energy for cellular renovation and homeostasis. Loss of autophagy is associated with cardiovascular diseases. Caveolin-3 (Cav-3), a muscle-specific isoform, is a structural protein within caveolae and is critical to stress adaptation in the heart. Whether Cav-3 plays a role in regulating autophagy to modulate cardiac stress responses remains unknown. In the present study, we used HL-1 cells, a cardiac muscle cell line, with stable Cav-3 knockdown (Cav-3 KD) and Cav-3 over-expression (Cav-3 OE) to study the impact of Cav-3 in regulation of autophagy...
October 5, 2016: American Journal of Physiology. Cell Physiology
Jianqiang Hu, Lei Zhang, Yang Yang, Yanjie Guo, Yanhong Fan, Mingming Zhang, Wanrong Man, Erhe Gao, Wei Hu, Russel J Reiter, Haichang Wang, Dongdong Sun
Melatonin reportedly protects against several cardiovascular diseases including ischemia/reperfusion (I/R), atherosclerosis and hypertension. The present study investigated the effects and mechanisms of melatonin on cardiomyocyte autophagy, apoptosis and mitochondrial injury in the context of MI. We demonstrated that melatonin significantly alleviated cardiac dysfunction after MI. Four weeks after MI, echocardiography and Masson staining indicated that melatonin notably mitigated adverse left ventricle remodeling...
October 1, 2016: Journal of Pineal Research
Mingyi Zhao, Ping Zhu, Masayuki Fujino, Yoshiaki Nishio, Jimei Chen, Hidenori Ito, Kiwamu Takahashi, Motowo Nakajima, Tohru Tanaka, Lingling Zhao, Jian Zhuang, Xiao-Kang Li
BACKGROUND: Hypoxia causes cardiac disease via oxidative stress and mitochondrial dysfunction. 5-Aminolevulinic acid in combination with sodium ferrous citrate (ALA/SFC) has been shown to up-regulate heme oxygenase-1 (HO-1) and decrease macrophage infiltration and renal cell apoptosis in renal ischemia injury mice. However, its underlying mechanism remains largely unknown. The aim of this study was to investigate whether ALA/SFC could protect cardiomyocytes from hypoxia-induced apoptosis by autophagy via HO-1 signaling...
October 28, 2016: Biochemical and Biophysical Research Communications
Amani Cherif-Sayadi, Kaouther Hadj Ayed-Tka, Mohamed Bejaoui, Neyla Ben Gdara, Mohamed Amine Zaouali, Hassen Ben Abdennebi
BACKGROUND The ability of nitrite to provide protection following ischemia/reperfusion (I/R) has been demonstrated, but its mechanism is still poorly understood. This study aimed to determine the optimal nitrite concentration to add into Institut Georges Lopez (IGL-1) storage solution and to assess its effect on antioxidant enzymes and autophagy. MATERIAL AND METHODS Livers from Sprague-Dawley rats were conserved in IGL-1 for 24 hours at 4°C or in IGL-1 enriched with nitrite at 50, 500 and 1,000 nM, respectively, before being perfused ex-vivo at 37 °C for 120 minutes...
2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Chao Nie, Jie Zhou, Xiaokang Qin, Xianming Shi, Qingqi Zeng, Jia Liu, Shihai Yan, Lei Zhang
Diosgenin, a plant steroid compound from Dioscorea nipponica, is an anti-inflammatory, antidiabetic, antitumor, vasodilatory compound, which also reduces blood lipid content and protects against ischemia‑induced neuronal damage. However, a limited number of studies have been performed on the antitumor effect of diosgenin on prostate cancer, the underlying mechanism of which remains to be fully elucidated. In the present study, the effect and underlying mechanism of diosgenin on DU145 human prostate cancer cells was investigated...
September 19, 2016: Molecular Medicine Reports
Jue Wang, Dong Han, Miao Sun, Juan Feng
Cerebral ischemic postconditioning (IPOC) has been demonstrated to be neuroprotective against cerebral ischemia reperfusion injury. The present study aimed to determine whether IPOC could inhibit autophagy and high mobility group box 1 (HMGB1) release in a PC12 cell oxygen glucose deprivation/reperfusion (OGD/R) model. An 8 h OGD and 24 h reperfusion cellular model was developed to mimic cerebral ischemia reperfusion injury, with 3 cycles of 10 min OGD/5 min reperfusion treatment to imitate IPOC. Cell viability was determined to demonstrate the efficiency of OGD/R, IPOC and autophagy activator, rapamycin (RAP), treatment...
September 19, 2016: Molecular Medicine Reports
Farinoosh Fakharnia, Fariba Khodagholi, Leila Dargahi, Abolhassan Ahmadiani
The mitochondrial permeability transition pore (mPTP) is a complex channel of the inner membrane, the opening of which leads to mitochondrial swelling and dissipation of mitochondrial membrane potential (MMP). Here, we aimed to evaluate the role of the cyclophilin D (CypD) as a prominent mediator of mPTP, on necroptosis and autophagy as well as apoptosis, beyond the global cerebral ischemia-reperfusion (I/R) injury. We showed that while cerebral I/R injury is accompanied by loss of MMP, mitochondrial swelling and programmed cell death, pretreatment with cyclosporine-A (CsA) as a potent inhibitor of CypD, led to partial but significant reduction in necroptosis markers, RIP1 and RIP3 as well as activity of glutamate-ammonia ligase (GLUL) and glutamate dehydrogenase 1 (GLUD1), downstream enzymes of RIP3...
September 23, 2016: Journal of Molecular Neuroscience: MN
Sheng Liu, Jun Zhang, Bentong Yu, Lei Huang, Bin Dai, Jichun Liu, Jian Tang
BACKGROUND: The aim of this study was to explore the role of autophagy in the cold I/R injury following lung transplantation. METHODS: The rat orthotopic lung transplantation model was established to perform the level of autophagy in the cold I/R injury in this study. The pretreatment of inhibitor (3-Methyladenine [3-MA]) and activator (rapamycin [RAPA]) of autophagy were performed to assess the role of autophagy in the cold I/R injury following lung transplantation in rats...
2016: American Journal of Translational Research
Jianjie Qin, Junjin Zhou, Xinzheng Dai, Haoming Zhou, Xiongxiong Pan, Xuehao Wang, Feng Zhang, Jianhua Rao, Ling Lu
Calorie restriction or starvation (fasting) has some beneficial effects in terms of prolonging life and increasing resistance to stress. It has also been shown that calorie restriction has a protective role during ischemia-reperfusion injury (IRI) in several organs, but the underlying mechanism has not been elucidated. In this study we investigated the effects and molecular mechanisms of short-term starvation (STS) on liver IRI in a mouse liver IRI model. We found that STS significantly attenuated liver IRI in this model, as evidenced by inhibition of serum aminotransferase levels, and decreased pathological damage and hepatocellular apoptosis, especially after 2- or 3-day starvation...
2016: American Journal of Translational Research
Wei Ruan, Qing Liu, Chan Chen, Suobei Li, Junmei Xu
OBJECTIVE: To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms.
 METHODS: Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min-
reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC...
September 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Hai-Jun Bao, Hai-Yang Qiu, Jin-Xia Kuai, Cheng-Jie Song, Shao-Xian Wang, Chao-Qun Wang, Hua-Bin Peng, Wen-Can Han, Yong-Ping Wu
The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis...
July 2016: Neural Regeneration Research
Yi-Hao Deng, Hong-Yun He, Li-Qiang Yang, Peng-Yue Zhang
The temporal dynamics of neuronal autophagy and apoptosis in the ischemic penumbra following stroke remains unclear. Therefore, in this study, we investigated the dynamic changes in autophagy and apoptosis in the penumbra to provide insight into potential therapeutic targets for stroke. An adult Sprague-Dawley rat model of permanent ischemic stroke was prepared by middle cerebral artery occlusion. Neuronal autophagy and apoptosis in the penumbra post-ischemia were evaluated by western blot assay and immunofluorescence staining with antibodies against LC3-II and cleaved caspase-3, respectively...
July 2016: Neural Regeneration Research
Mikko T Huuskonen, Sanna Loppi, Hiramani Dhungana, Velta Keksa-Goldsteine, Sighild Lemarchant, Paula Korhonen, Sara Wojciechowski, Eveliina Pollari, Piia Valonen, Juho Koponen, Akihiko Takashima, Gary Landreth, Gundars Goldsteins, Tarja Malm, Jari Koistinaho, Katja M Kanninen
Stroke is a highly debilitating, often fatal disorder for which current therapies are suitable for only a minor fraction of patients. Discovery of novel, effective therapies is hampered by the fact that advanced age, primary age-related tauopathy or comorbidities typical to several types of dementing diseases are usually not taken into account in preclinical studies, which predominantly use young, healthy rodents. Here we investigated for the first time the neuroprotective potential of bexarotene, an FDA-approved agent, in a co-morbidity model of stroke that combines high age and tauopathy with thromboembolic cerebral ischemia...
2016: Scientific Reports
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