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heme oxygenase and autophagy

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https://www.readbyqxmd.com/read/29241092/trehalose-protects-against-oxidative-stress-by-regulating-the-keap1-nrf2-and-autophagy-pathways
#1
Yuhei Mizunoe, Masaki Kobayashi, Yuka Sudo, Shukoh Watanabe, Hiromine Yasukawa, Daiki Natori, Ayana Hoshino, Arisa Negishi, Naoyuki Okita, Masaaki Komatsu, Yoshikazu Higami
Dysfunction of autophagy, which regulates cellular homeostasis by degrading organelles and proteins, is associated with pathogenesis of various diseases such as cancer, neurodegeneration and metabolic disease. Trehalose, a naturally occurring nontoxic disaccharide found in plants, insects, microorganisms and invertebrates, but not in mammals, was reported to function as a mechanistic target of the rapamycin (mTOR)-independent inducer of autophagy. In addition, trehalose functions as an antioxidant though its underlying molecular mechanisms remain unclear...
September 20, 2017: Redox Biology
https://www.readbyqxmd.com/read/29235250/discovery-and-mechanistic-elucidation-of-a-class-of-pdi-inhibitors-for-the-treatment-of-glioblastoma
#2
Anahita Kyani, Shuzo Tamura, Suhui Yang, Andrea Shergalis, Soma Somanta, Yuting Kuang, Mats Ljungman, Nouri Neamati
Protein disulfide isomerase (PDI) is overexpressed in glioblastoma, the most aggressive form of brain cancer, and folds nascent proteins responsible for the progression and spread of the disease. Herein, we describe a novel, nanomolar PDI inhibitor, pyrimidotriazinedione 35G8, that is toxic in a panel of human glioblastoma cell lines. We performed a medium throughput 20,000-compound screen of a diverse subset of 1,000,000 compounds to identify cytotoxic small molecules. Cytotoxic compounds were screened for PDI inhibition, and, from the screen, 35G8 emerged as the most cytotoxic inhibitor of PDI...
December 12, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29152091/fibroblast-growth-factor-2-mediated-protection-of-cardiomyocytes-from-the-toxic-effects-of-doxorubicin-requires-the-mtor-nrf-2-ho-1-pathway
#3
Navid Koleini, Barbara E Nickel, Jie Wang, Zeinab Roveimiab, Robert R Fandrich, Lorrie A Kirshenbaum, Peter A Cattini, Elissavet Kardami
Background: Cardiotoxic side effects impose limits to the use of anti-tumour chemotherapeutic drugs such as doxorubicin (Dox). There is a need for cardioprotective strategies to prevent the multiple deleterious effects of Dox. Here, we examined the ability of administered fibroblast growth factor-2 (FGF-2), a cardioprotective protein that is synthesized as high and low molecular weight (Hi-, Lo-FGF-2) isoforms, to prevent Dox-induced: oxidative stress; cell death; lysosome dysregulation; and inactivation of potent endogenous protective pathways, such as the anti-oxidant/detoxification nuclear factor erythroid-2-related factor (Nrf-2), heme oxygenase-1 (HO-1) axis...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136322/heme-oxygenase-1-regulates-sirtuin-1-autophagy-pathway-in-liver-transplantation-from-mouse-to-human
#4
Kojiro Nakamura, Shoichi Kageyama, Shi Yue, Jing Huang, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Liver ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although graft autophagy is essential for resistance against hepatic IRI, its significance in clinical OLT remains unknown. Despite recent data identifying heme oxygenase-1 (HO-1) as a putative autophagy inducer, its role in OLT and interactions with Sirtuin-1 (SIRT1), a key autophagy regulator, have not been studied. We aimed to examine HO-1 mediated autophagy induction in human OLT and in a murine OLT model with extended (20h) cold storage, as well as to analyze the requirement for SIRT1 in autophagy regulation by HO-1...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29128799/fty720-inhibits-the-nrf2-are-pathway-in-human-glioblastoma-cell-lines-and-sensitizes-glioblastoma-cells-to-temozolomide
#5
Li Zhang, Handong Wang
BACKGROUND: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor regulating the expression of various cytoprotective genes. Constitutive Nrf2 activation in many cancers enhances cell survival and resistance to anti-cancer drugs. Our previous studies have shown that FTY720 induced autophagy-related apoptosis and necroptosis and inhibited invasion and migration in human glioblastoma cells. However, whether FTY720 regulated Nrf2 in glioblastoma cells remained unclear...
July 4, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29091860/eclalbasaponin-i-from-aralia-elata-miq-seem-reduces-oxidative-stress-induced-neural-cell-death-by-autophagy-activation
#6
Wei Wang, Guo-Dong Yao, Xin-Yue Shang, Ji-Chao Gao, Yan Zhang, Shao-Jiang Song
Oxidative stress has been proposed to contribute to DNA damage and is involved in many neurodegenerative diseases. It has been reported that Aralia elata (Miq.) Seem. (A. elata) exhibits an anti-oxidative effect but the mechanisms underlying this protective effect are still unclear. In this study, six known triterpene saponins were isolated from the buds of A. elata, a well-known medicinal and edible plant in Northeast China. Subsequently, the anti-oxidative effects of all six triterpene saponins were screened by H2O2-induced damage in human neuronblastoma SH-SY5Y cells...
October 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28944924/cyclic-helix-b-peptide-protects-hk%C3%A2-2-cells-from-oxidative-stress-by-inhibiting-er-stress-and-activating-nrf2-signalling-and-autophagy
#7
Long Li, Miao Lin, Lexi Zhang, Shang Huang, Chao Hu, Long Zheng, Liping Li, Chao Zhang, Cheng Yang, Yaqiu Long, Ruiming Rong, Tongyu Zhu
Renal ischemia‑reperfusion injury (IRI) is present in numerous diseases and is observed following certain treatments, including renal transplantation. Preventing tubular epithelial cells (TECs) from undergoing apoptosis is vital for treatment of renal IRI. Cyclic helix B peptide (CHBP) is a novel agent that has a protective effect on renal IRI in vivo. In the present study, the effect and underlying mechanism of CHBP on TECs was investigated. The HK‑2 human renal proximal tubular epithelial cell line was treated with 500 µmol/l H2O2 for 4 h prior to determining the effect of CHBP pretreatment for 1 h on cell viability, caspase 3 activity and expression levels, expression levels of oxidative stress markers, endoplasmic reticulum (ER) stress markers, NF‑E2‑related factor 2 (Nrf2), heme oxygenase‑1 (HO‑1) and autophagy markers...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28940469/cytoprotective-effects-of-xanthohumol-against-methylglyoxal-induced-cytotoxicity-in-mc3t3-e1-osteoblastic-cells
#8
Kwang Sik Suh, Suk Chon, Eun Mi Choi
Methylglyoxal (MG) has been suggested to be a major source of intracellular reactive carbonyl compounds, and has been implicated in increasing the levels of advanced glycation end products in age-related diseases. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. In the present study, we investigated the effects of xanthohumol on MG-induced cytotoxicity in osteoblastic MC3T3-E1 cells. Xanthohumol attenuated MG-induced cytotoxicity, as evidenced by improved cell viability, and prevented MG-induced MG-protein adducts, inflammatory cytokines, reactive oxygen species and mitochondrial superoxide production...
September 20, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28901391/protective-effects-of-heme-oxygenase-1-transduced-bone-marrow-derived-mesenchymal-stem-cells-on-reduced%C3%A2-size-liver-transplantation-role-of-autophagy-regulated-by-the-erk-mtor-signaling-pathway
#9
Raorao Wang, Zhongyang Shen, Liu Yang, Mingli Yin, Weiping Zheng, Bin Wu, Tao Liu, Hongli Song
Autophagy is a critical lysosomal pathway that degrades cytoplasmic components to maintain cell homeostasis and provide substrates for energy metabolism. A study revealed that heme oxygenase-1 (HO-1)-transduced bone marrow-derived mesenchymal stem cells (BM-MSCs) could protect 50% reduced-size liver transplantation (RSLT) in a rat model. However, the mechanisms remain mostly unknown. The aim of the present study was to explore the effects and related mechanism of autophagy on the protection conferred by HO-1-transduced BM-MSCs (HO-1/BM-MSCs) on 50% RSLT in a rat model...
November 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28846887/attenuation-of-cyclosporine-a-induced-nephrotoxicity-by-schisandrin-b-through-suppression-of-oxidative-stress-apoptosis-and-autophagy
#10
Qiao Lai, Zhengzhong Luo, Chunying Wu, Sisi Lai, Hanmei Wei, Tongming Li, Qing Wang, Yang Yu
Cyclosporine A (CsA) is a potent immunosuppressive agent whose clinical usage is limited by nephrotoxicity. Schisandrin B (SchB), isolated from the fruit of Schisandra chinensis, is a natural compound with multiple pharmacological activities that has been shown to attenuate organ injury caused by CsA. Hence, the primary objective of the current study was to evaluate whether SchB has a cytoprotective effect on CsA-induced nephrotoxicity in human proximal tubular epithelial cell line (HK-2). This study demonstrated that pre-incubation of HK-2 cells with 2...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28802142/overexpression-of-ho-1-assisted-pm2-5-induced-apoptosis-failure-and-autophagy-related-cell-necrosis
#11
Wei Zhou, Xiaoyan Yuan, Li Zhang, Baoting Su, Dongdong Tian, Yang Li, Jun Zhao, Yimei Wang, Shuangqing Peng
Severe smog/haze events accompanied by extremely high concentrations of airborne fine particulate matter (PM2.5) have emerged frequently in China and the potential health risks have attracted ever-growing attention. During these episodes, a surge in hospital visits for acute respiratory symptoms and respiratory diseases exacerbation has been reported to be associated with acute exposure to high-levels of particulate matters. To investigate cell fate determination and the underlying pathogenic mechanisms during severe haze episodes or smog events, we exposed human lung epithelial cells (BEAS-2B) to PM2...
August 9, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28782507/mapk-jnk1-activation-protects-cells-against-cadmium-induced-autophagic-cell-death-via-differential-regulation-of-catalase-and-heme-oxygenase-1-in-oral-cancer-cells
#12
Keum-Young So, Sang-Hun Kim, Ki-Tae Jung, Hyun-Young Lee, Seon-Hee Oh
Antioxidant enzymes are related to oral diseases. We investigated the roles of heme oxygenase-1 (HO-1) and catalase in cadmium (Cd)-induced oxidative stress and the underlying molecular mechanism in oral cancer cells. Exposing YD8 cells to Cd reduced the expression levels of catalase and superoxide dismutase 1/2 and induced the expression of HO-1 as well as autophagy and apoptosis, which were reversed by N-acetyl-l-cysteine (NAC). Cd-exposed YD10B cells exhibited milder effects than YD8 cells, indicating that Cd sensitivity is associated with antioxidant enzymes and autophagy...
October 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28627343/-study-on-the-role-of-autophagy-in-heme-oxygenase-1-preventing-hepatic-ischemia-reperfusion-injury-in-rats
#13
Sheng Lan, Jintai Li, Yi Liu
OBJECTIVE: To identify the role of autopahgy in the protective mechanism of heme oxygenase 1 (HO-1) against hepatic ischemia/reperfusion (I/R) injury. METHODS: Forty healthy male Sprague-Dawley (SD) rats were randomly (random number table) divided into five groups (n = 8 in each group), namely sham group, model group, cobalt protoporphyrin (CoPP) group, zinc protoporphyrin (ZnPP) group and 6-amino-3-methylpurine (3-MA) group. Partial hepatic I/R model was established by clamping the pedicles of left and median lobes for 1 hour and reopening for 6 hours in rats, and the rats in sham group were only received celiotomp without hepatic I/R...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28596808/saturated-hydrogen-saline-ameliorates-lipopolysaccharide-induced-acute-lung-injury-by-reducing-excessive-autophagy
#14
Yiming Liu, Jin Zhang
The pathogenesis of acute lung injury (ALI) induced by lipopolysaccharide (LPS) involves excessive pulmonary inflammation and oxidative stress. In turn, autophagy is associated with inflammatory diseases and organ dysfunction, and studies have demonstrated that LPS treatment may trigger autophagy. Thus, excessive autophagy may stimulate the strong inflammatory response observed in the development of LPS-induced ALI. Saturated hydrogen saline may alleviate LPS-induced ALI by inhibiting autophagy, however its underlying mechanisms of action remain unknown...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28578014/carbon-monoxide-protects-against-hepatic-steatosis-in-mice-by-inducing-sestrin-2-via-the-perk-eif2%C3%AE-atf4-pathway
#15
Hyo Jeong Kim, Yeonsoo Joe, Seul-Ki Kim, Se-Ung Park, Jeongmin Park, Yingqing Chen, Jin Kim, Jinhyun Ryu, Gyeong Jae Cho, Young-Joon Surh, Stefan W Ryter, Uh-Hyun Kim, Hun-Taeg Chung
Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has emerged as one of the most common causes of chronic liver disease in developed countries over the last decade. NAFLD comprises a spectrum of pathological hepatic changes, including steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Autophagy, a homeostatic process for protein and organelle turnover, is decreased in the liver during the development of NAFLD. Previously, we have shown that carbon monoxide (CO), a reaction product of heme oxygenase (HO) activity, can confer protection in NAFLD, though the molecular mechanisms remain unclear...
May 31, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28524859/mesenchymal-stem-cells-sense-mitochondria-released-from-damaged-cells-as-danger-signals-to-activate-their-rescue-properties
#16
Meriem Mahrouf-Yorgov, Lionel Augeul, Claire Crola Da Silva, Maud Jourdan, Muriel Rigolet, Sylvie Manin, René Ferrera, Michel Ovize, Adeline Henry, Aurélie Guguin, Jean-Paul Meningaud, Jean-Luc Dubois-Randé, Roberto Motterlini, Roberta Foresti, Anne-Marie Rodriguez
Mesenchymal stem cells (MSCs) protect tissues against cell death induced by ischemia/reperfusion insults. This therapeutic effect seems to be controlled by physiological cues released by the local microenvironment following injury. Recent lines of evidence indicate that MSC can communicate with their microenvironment through bidirectional exchanges of mitochondria. In particular, in vitro and in vivo studies report that MSCs rescue injured cells through delivery of their own mitochondria. However, the role of mitochondria conveyed from somatic cells to MSC remains unknown...
July 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28482861/therapeutic-effect-of-urine-derived-stem-cells-for-protamine-lipopolysaccharide-induced-interstitial-cystitis-in-a-rat-model
#17
Jia Li, Hui Luo, Xingyou Dong, Qian Liu, Chao Wu, Teng Zhang, Xiaoyan Hu, Yuanyuan Zhang, Bo Song, Longkun Li
BACKGROUND: Interstitial cystitis (IC) is a chronic inflammation disorder mainly within the submucosal and muscular layers of the bladder. As the cause of IC remains unknown, no effective treatments are currently available. Administration of stem cell provides a potential for treatment of IC. METHODS: This study was conducted using urine-derived stem cells (USCs) for protamine/lipopolysaccharide (PS/LPS)-induced interstitial cystitis in a rodent model. In total, 60 female Sprague-Dawley rats were randomized into three experimental groups (n = 5/group): sham controls; IC model alone; and IC animals intravenously treated with USCs (1...
May 8, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28420170/fisetin-protects-pc12-cells-from-tunicamycin-mediated-cell-death-via-reactive-oxygen-species-scavenging-and-modulation-of-nrf2-driven-gene-expression-sirt1-and-mapk-signaling-in-pc12-cells
#18
Jui-Hung Yen, Pei-Shan Wu, Shu-Fen Chen, Ming-Jiuan Wu
BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28194437/mitochondrial-quality-control-dysregulation-in-conditional-ho-1-mice
#19
Hagir B Suliman, Jeffrey E Keenan, Claude A Piantadosi
The heme oxygenase-1 (Hmox1; HO-1) pathway was tested for defense of mitochondrial quality control in cardiomyocyte-specific Hmox1 KO mice (HO-1[CM](-/-)) exposed to oxidative stress (100% O2). After 48 hours of exposure, these mice showed persistent cardiac inflammation and oxidative tissue damage that caused sarcomeric disruption, cardiomyocyte death, left ventricular dysfunction, and cardiomyopathy, while control hearts showed minimal damage. After hyperoxia, HO-1(CM)(-/-) hearts showed suppression of the Pgc-1α/nuclear respiratory factor-1 (NRF-1) axis, swelling, low electron density mitochondria by electron microscopy (EM), increased cell death, and extensive collagen deposition...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28188022/interplay-between-hsp90-and-nrf2-pathways-in-diabetes-associated-atherosclerosis
#20
Iolanda Lazaro, Ainhoa Oguiza, Carlota Recio, Laura Lopez-Sanz, Susana Bernal, Jesus Egido, Carmen Gomez-Guerrero
INTRODUCTION: Oxidative stress and inflammation are determinant processes in the development of diabetic vascular complications. Heat shock protein 90 (HSP90) overexpression in atherosclerotic plaques plays a role in sustaining inflammatory mechanisms, and its specific inhibition prevents atherosclerosis. The present work investigates, in a mouse model of diabetes-driven atherosclerosis, whether atheroprotection by pharmacological HSP90 inhibition is accomplished by bolstering antioxidant defense mechanisms headed by nuclear factor erythroid-derived 2-like 2 (Nrf2)...
March 2017: Clínica e Investigación en Arteriosclerosis
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