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heme oxygenase and autophagy

M Chevallet, B Gallet, A Fuchs, P H Jouneau, K Um, E Mintz, I Michaud-Soret
Increased production and use of zinc oxide nanoparticles (ZnO-NPs) in consumer products has prompted the scientific community to investigate their potential toxicity, and understand their impact on the environment and organisms. Molecular mechanisms involved in ZnO-NP toxicity are still under debate and focus essentially on high dose expositions. In our study, we chose to evaluate the effect of sub-toxic doses of ZnO-NPs on human hepatocytes (HepG2) with a focus on metal homeostasis and redox balance disruptions...
October 26, 2016: Nanoscale
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
Keum-Young So, Seon-Hee Oh
Heme oxygenase-1 (HO-1) protects cells against cadmium (Cd)-induced oxidative stress. However, the mechanism underlying this protection is not well understood. In this study, we elucidated the role of HO-1 in Cd-induced cytotoxicity. Exposure of NRK52E cells to Cd induced protein kinase B (PKB)/Akt, protein kinase C (PKC)-δ, and glycogen synthase kinase (GSK) 3αb phosphorylation, and eukaryotic initiation factor (eIF) 2α dephosphorylation. Pharmacological inhibition of Akt resulted in HO-1 suppression and eIF2α activation, which partially suppressed CHOP and PARP-1 cleavage, but promoted autophagy and decreased cell viability...
September 20, 2016: Toxicology
Jeong-Seok Kim, Young-Hee Lee, Ho-Keun Yi
Recent evidence suggests that autophagy and bone morphogenetic protein signaling pathway regulate skeletal muscle growth and bone formation in aged rats. However, the effect of downhill running on muscle growth and bone formation is not well understood. Thus, we investigated the effect of downhill and uphill running on age-related muscle and bone weakness. Young and late middle-aged rats were randomly assigned to control groups; young (YC) and late middle-aged (LMC), and two types of running training groups: late middle-aged downhill (LMD) and late middle-aged uphill (LMU)...
September 19, 2016: Experimental Physiology
Nan Hu, Jun Ren, Yingmei Zhang
Insulin resistance contributes to the high prevalence of type 2 diabetes mellitus, leading to cardiac anomalies. Emerging evidence depicts a pivotal role for mitochondrial injury in oxidative metabolism and insulin resistance. Mitochondrial aldehyde dehydrogenase (ALDH2) is one of metabolic enzymes detoxifying aldehydes although its role in insulin resistance remains elusive. This study was designed to evaluate the impact of ALDH2 overexpression on insulin resistance-induced myocardial damage and mechanisms involved with a focus on autophagy...
September 12, 2016: Oncotarget
Keum-Young So, Seon-Hee Oh
Heme oxygenase-1 (HO-1) is a stress-inducible cytoprotective enzyme. It is often overexpressed in different types of cancers and promotes cell survival. However, the role of HO-1 and the underlying molecular mechanism of cadmium (Cd)-induced oxidative stress in cancer cells remain undefined. Here we show that the role of HO-1 under Cd-induced oxidative stress is dependent upon autophagy, which is sensitized by the tumor suppressor p53. The sensitivity to Cd was 3.5- and 14-fold higher in p53-expressing YD8 and H460 cells than in p53-null YD10B and H1299 cells, respectively...
October 7, 2016: Biochemical and Biophysical Research Communications
Shin Sato, Saori Kataoka, Akane Kimura, Yuuka Mukai
Diabetic kidney disease is associated with oxidative stress, inflammation, and autophagy. The aim of this study was to investigate the effect of azuki bean (Vigna angularis) extract (ABE) on oxidative stress and autophagy in the kidneys of diabetic rats. Streptozotocin (STZ)-induced diabetic rats received 0, 10, or 40 mg/kg of ABE orally for 4 weeks, whereas vehicle-injected control rats received distilled water. Level of plasma glutathione and expression of heme oxygenase-1 (HO-1), p47phox (NADPH oxidase subunit), and markers associated with autophagy were examined...
July 5, 2016: Canadian Journal of Physiology and Pharmacology
Jésica Flores-Martín, Luciana Reyna, Magali E Ridano, Graciela M Panzetta-Dutari, Susana Genti-Raimondi
StarD7 is an intracellular lipid transport protein identified as up-regulated in the choriocarcinoma JEG-3 cell line. StarD7 facilitates the delivery of phosphatidylcholine (PC) to the mitochondria, and StarD7 knockdown causes a reduction in phospholipid synthesis. Since inhibition of PC synthesis may lead to endoplasmic reticulum (ER) stress we hypothesized that StarD7 may be involved in maintaining cell homeostasis. Here, we examined the effect of StarD7 silencing on ER stress response and on the levels of reactive oxygen species (ROS) in the human hepatoma cell line HepG2...
August 20, 2016: Free Radical Biology & Medicine
Qian Zhou, Bin Chen, Xindong Wang, Lixin Wu, Yang Yang, Xiaolan Cheng, Zhengli Hu, Xueting Cai, Jie Yang, Xiaoyan Sun, Wuguang Lu, Huaijiang Yan, Jiao Chen, Juan Ye, Jianping Shen, Peng Cao
Sulforaphane, a naturally occurring compound found in cruciferous vegetables, has been shown to be neuroprotective in several neurological disorders. In this study, we sought to investigate the potential protective effects and associated molecular mechanisms of sulforaphane in an in vivo Parkinson's disease (PD) model, based on rotenone-mediated neurotoxicity. Our results showed that sulforaphane inhibited rotenone-induced locomotor activity deficiency and dopaminergic neuronal loss. Additionally, sulforaphane treatment inhibited the rotenone-induced reactive oxygen species production, malondialdehyde (MDA) accumulation, and resulted in an increased level of total glutathione and reduced glutathione (GSH): oxidized glutathione (GSSG) in the brain...
2016: Scientific Reports
Sachi Shibata, Hiroyuki Ishitobi, Shigeru Miyaki, Tomohiro Kawaoka, Tomoko Kayashima, Kiminori Matsubara
Carnosic acid (CA) is recognized as a unique neuroprotective compound in the herb rosemary, since it induces expression of antioxidant enzymes including heme oxygenase-1 (HO-1), γ-glutamylcysteine synthase (γ-GCS), and glutathione S-transferase (GST) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a nuclear transcription factor. In this study, we examined the cytoprotective effects of CA against starvation. We found that CA protected starvation-induced SH-SY5Y cell death by activating Akt and extracellular signal-regulated kinase 1/2 (Erk1/2)...
December 2016: International Journal of Food Sciences and Nutrition
Timothé Denaës, Jasper Lodder, Marie-Noële Chobert, Isaac Ruiz, Jean-Michel Pawlotsky, Sophie Lotersztajn, Fatima Teixeira-Clerc
Kupffer cells, the resident macrophages of the liver, play a major role in the pathogenesis of alcoholic liver disease. We have previously demonstrated that CB2 receptor protects against alcoholic liver disease by inhibiting alcohol-induced inflammation and steatosis via the regulation of Kupffer cell activation. Here, we explored the mechanism underlying these effects and hypothesized that the anti-inflammatory properties of CB2 receptor in Kupffer cells rely on activation of autophagy. For this purpose, mice invalidated for CB2 receptor (CB2(Mye-/-) mice) or for the autophagy gene ATG5 (ATG5(Mye-/-) mice) in the myeloid lineage, and their littermate wild-type mice were subjected to chronic-plus-binge ethanol feeding...
2016: Scientific Reports
Shuichiro Okamoto, Takayuki Tsujioka, Shin-Ichiro Suemori, Jun-Ichiro Kida, Toshinori Kondo, Yumi Tohyama, Kaoru Tohyama
Treatment outcomes for acute myeloid leukemia and myelodysplastic syndromes (MDS) remain unsatisfactory despite progress in various types of chemotherapy and hematopoietic stem cell transplantation. Therefore, there is a need for the development of new treatment options. We investigated the growth-suppressive effects of withaferin A (WA), a natural plant steroidal lactone, on myelodysplasia and leukemia cell lines. WA exhibited growth-suppressive effects on the cell lines, MDS-L, HL-60, THP-1, Jurkat and Ramos, and induction of cell cycle arrest at G2/M phase at relatively low doses...
September 2016: Cancer Science
Li-Fang Wang, Kazunari K Yokoyama, Chih-Lung Lin, Tzu-Yin Chen, Hsiu-Wen Hsiao, Pei-Chi Chiang, Chin Hsu
Men have worse survival than premenopausal women after intracerebral hemorrhage (ICH). After ICH, overproduction of iron associated with induction of heme oxygenase-1 (HO-1) in brain was observed. Rodent ICH model using ferrous citrate (FC)-infusion into the striatum to simulate iron overload, showed a higher degree of injury severity in males than in females. However, the participation of HO-1 in sex-differences of iron-induced brain injury remains unknown. The present results showed a higher level of HO-1 expression associated with more severe injury in males compared with females after FC-infusion...
2016: Scientific Reports
Caitlyn R Scharn, Angela C Collins, Vidhya R Nair, Chelsea E Stamm, Denise K Marciano, Edward A Graviss, Michael U Shiloh
Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that M. tuberculosis infection in mice induces expression of the CO-producing enzyme heme oxygenase (HO1) and that CO is sensed by M. tuberculosis to initiate a dormancy program. Further, mice deficient in HO1 succumb to M. tuberculosis infection more readily than do wild-type mice. Although mouse macrophages control intracellular M. tuberculosis infection through several mechanisms, such as NO synthase, the respiratory burst, acidification, and autophagy, how human macrophages control M...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Anding Liu, Liang Huang, Enshuang Guo, Renlong Li, Jiankun Yang, Anyi Li, Yan Yang, Shenpei Liu, Jifa Hu, Xiaojing Jiang, Olaf Dirsch, Uta Dahmen, Jian Sun
We previously demonstrated that baicalein could protect against liver ischemia/reperfusion (I/R) injury in mice. The exact mechanism of baicalein remains poorly understood. Autophagy plays an important role in protecting against I/R injury. This study was designed to determine whether baicalein could protect against liver I/R injury via induction of autophagy in rats. Baicalein was intraperitoneally injected 1 h before warm ischemia. Pretreatment with baicalein prior to I/R insult significantly blunted I/R-induced elevations of serum aminotransferase levels and significantly improved the histological status of livers...
2016: Scientific Reports
Jia Xu, Jinshun Li, Jinhua Wang, Yanchun Chi, Kun Zhang, Rui Cui
Increasing evidence has demonstrated that the activation of heme oxygenase (HO)‑1 reduces autophagy stimulated by oxidative stress injury, in which the supraphysiological production of reactive oxygen species (ROS) is detected. However, the potential mechanism underlying this effect remains unclear. The present study aimed to investigate the function of HO‑1 activation in the regulation of autophagy in glomerular mesangial cells subjected to H2O2‑induced oxidative stress injury. The results demonstrated that the HO‑1 agonist, hemin, reduces the LC3 protein level, which was enhanced by H2O2 treatment...
June 2016: Molecular Medicine Reports
Lu Cao, Jishi Wang, Dan Ma, Ping Wang, Yaming Zhang, Qin Fang
Heme oxygenase-1 (HO-1) has been verified to play an important role in imatinib (IM)-resistant chronic myeloid leukemia (CML) cells, but the mechanism remains unclear. In drug resistant CML cells, HO-1 expression abnormally increased and that of autophagy-related protein LC-3I/II also increased, so we herein postulated HO-1 was associated with autophagy. HO-1 expressions in IM-sensitive/resistant K562/K562R cells were regulated through lentiviral mediation. K562 cells transfected with HO-1 resisted IM and underwent obvious autophagy...
March 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xiao-Feng Zhu, Wen Li, Jie-Yi Ma, Nan Shao, Yun-Jian Zhang, Rui-Ming Liu, Wei-Bin Wu, Ying Lin, Shen-Ming Wang
Heme oxygenase-1 (HMOX-1) is a microsomal enzyme that exerts anti-apoptotic and cytoprotective effects. In the present study, HMOX-1 was demonstrated to be overexpressed and able to be induced by doxorubicin in breast cancer cell lines. Knockdown of HMOX-1 using short interfering (si)RNA enhanced the cytotoxicity of doxorubicin in MDA-MB-231 and BT549 cells. Knockdown of HMOX-1 downregulated B cell lymphoma (Bcl)-2 and Bcl-extra large expression, and significantly enhanced doxorubicin-induced apoptosis in MDA-MB-231 and BT549 cells...
November 2015: Oncology Letters
Tsuyoshi Takada, Shigeru Miyaki, Hiroyuki Ishitobi, Yuya Hirai, Tomoyuki Nakasa, Kazuhiko Igarashi, Martin K Lotz, Mitsuo Ochi
INTRODUCTION: BTB and CNC homology 1 (Bach1) is a transcriptional repressor of Heme oxygenase-1 (HO-1), which is cytoprotective through its antioxidant effects. The objective of this study was to define the role of Bach1 in cartilage homeostasis and osteoarthritis (OA) development using in vitro models and Bach1 (-/-) mice. METHODS: HO-1 expression in Bach1 (-/-) mice was analyzed by real-time PCR, immunohistochemistry and immunoblotting. Knee joints from Bach1 (-/-) and wild-type mice with age-related OA and surgically-induced OA were evaluated by OA scoring systems...
October 13, 2015: Arthritis Research & Therapy
Qiao Lai, Jiabao Wei, Mohammed Mahmoodurrahman, Chenxue Zhang, Shijian Quan, Tongming Li, Yang Yu
Cyclosporine A (CsA) is a powerful immunosuppressive drug. However, nephrotoxicity resulting from its long-term usage has hampered its prolonged therapeutic usage. Schisandra chinensis extracts (SCE) have previously been used in traditional Chinese medicine and more recently coadministered with Western medicine for the treatment of CsA-induced side effects in the People's Republic of China. This study aimed to investigate the possible effects of SCE on the pharmacokinetics of CsA in rats and elucidate the potential mechanisms by which it hinders the development of CsA-induced nephrotoxicity...
2015: Drug Design, Development and Therapy
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