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heme oxygenase and autophagy

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https://www.readbyqxmd.com/read/29796178/sb202190-inhibits-endothelial-cell-apoptosis-via-induction-of-autophagy-and-heme-oxygenase-1
#1
Margit Schwartz, Sabine Böckmann, Philipp Borchert, Burkhard Hinz
Activation of the p38 mitogen-activated protein kinase (MAPK) pathway has been implicated in various detrimental events finally leading to endothelial dysfunction. The present study therefore investigates the impact of the p38 MAPK inhibitor SB202190 on the expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) as well as metabolic activity, apoptosis and autophagy of endothelial cells. Using human umbilical vein endothelial cells (HUVEC) SB202190 was found to cause a time- and concentration-dependent induction of HO-1 protein...
May 1, 2018: Oncotarget
https://www.readbyqxmd.com/read/29725710/activation-of-autophagic-flux-and-the-nrf2-are-signaling-pathway-by-hydrogen-sulfide-protects-against-acrylonitrile-induced-neurotoxicity-in-primary-rat-astrocytes
#2
Bobo Yang, Yu Bai, Changsheng Yin, Hai Qian, Guangwei Xing, Suhua Wang, Fang Li, Jinsong Bian, Michael Aschner, Rongzhu Lu
Hydrogen sulfide (H2 S), the third gasotransmitter, has been shown to act as a neuroprotective factor in numerous pathological processes; however, its underlying mechanism(s) of action remain unclear. It is widely accepted that activation of moderate autophagy and the Nrf2/ARE signaling pathway play important roles in the biological self-defense systems. In the present study, we investigated whether exogenous H2 S protects against the cytotoxicity of acrylonitrile (AN), a neurotoxin, in primary rat astrocytes...
May 3, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29570846/neuroprotective-effects-of-creatine-in-the-cmvmjd135-mouse-model-of-spinocerebellar-ataxia-type-3
#3
Sara Duarte-Silva, Andreia Neves-Carvalho, Carina Soares-Cunha, Joana M Silva, Andreia Teixeira-Castro, Rita Vieira, Anabela Silva-Fernandes, Patrícia Maciel
BACKGROUND AND OBJECTIVE: Mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Creatine administration increases concentration of the energy buffer phosphocreatine, exerting protective effects in the brain. We evaluate whether a creatine-enriched diet would be beneficial for a mouse model of spinocerebellar ataxia type 3, a genetically defined neurodegenerative disease for which no treatment is available. METHODS: We performed 2 independent preclinical trials using the CMVMJD135 mouse model (treating 2 groups of animals with different disease severity) and wild-type mice, to which 2% creatine was provided for 19 (preclinical trial 1) or 29 (preclinical trial 2) weeks, starting at a presymptomatic age...
March 23, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29550550/lactulose-attenuates-meth-induced-neurotoxicity-by-alleviating-the-impaired-autophagy-stabilizing-the-perturbed-antioxidant-system-and-suppressing-apoptosis-in-rat-striatum
#4
Xiao-Li Xie, Jie-Tao He, Zheng-Tao Wang, Huan-Qin Xiao, Wen-Tao Zhou, Si-Hao Du, Ye Xue, Qi Wang
Methamphetamine (METH) is a widely abused psychostimulant. Lactulose is a non-absorbable sugar, which effectively decreases METH-induced neurotoxicity in rat. However, the exact mechanisms need further investigation. In this study, 5-week-old male Sprague Dawley rats received METH (15 mg/kg, 8 intraperitoneal injections, 12-h interval) or saline and received lactulose (5.3 g/kg, oral gavage, 12-h interval) or vehicle 2 days prior to the METH administration. Compared to the control group, in the METH alone group, cytoplasmic vacuolar degeneration in hepatocytes, higher levels of alanine transaminase, aspartate transaminase and ammonia, overproduction of reactive oxygen species (ROS) and increase of superoxide dismutase activity in the blood were observed...
June 1, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29525531/raspberry-ketone-induces-brown-like-adipocyte-formation-through-suppression-of-autophagy-in-adipocytes-and-adipose-tissue
#5
Sy-Ying Leu, Yung-Chieh Tsai, Wen-Chi Chen, Chih-Hsiung Hsu, Yen-Mei Lee, Pao-Yun Cheng
Promoting white adipose tissue (WAT) to acquire brown-like characteristics is a promising approach for obesity treatment. Although raspberry ketone (RK) has been reported to possess antiobesity activity, its effects on the formation of brown-like adipocytes remain unclear. Therefore, we investigated the effects and underlying mechanism of RK on WAT browning in 3T3-L1 adipocytes and rats with ovariectomy (Ovx)-induced obesity. RK (100 μM) significantly induced browning of 3T3-L1 cells by increasing mitochondrial biogenesis and the expression of browning-specific proteins (PR domain containing 16, PRDM16; peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC-1α; uncoupling protein-1, UCP-1) and lipolytic enzymes (hormone-sensitive lipase and adipose triglyceride lipase)...
February 13, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29457983/antimycobacterial-effect-of-ifng-interferon-gamma-induced-autophagy-is-dependent-on-the-hmox1-heme-oxygenase-1-mediated-increase-in-the-intracellular-calcium-levels-and-modulation-of-ppp3-calcineurin-tfeb-transcription-factor-eb-axis
#6
Nisha Singh, Pallavi Kansal, Zeeshan Ahmad, Naveen Baid, Hariom Kushwaha, Neeraj Khatri, Ashwani Kumar
IFNG (interferon gamma)-induced autophagy plays an important role in the elimination of intracellular pathogens, such as Mycobacterium tuberculosis (Mtb). However, the signaling cascade that leads to the increase in autophagy flux in response to IFNG is poorly defined. Here, we demonstrate that HMOX1 (heme oxygenase 1)-generated carbon monoxide (CO) is required for the induction of autophagy and killing of Mtb residing in macrophages in response to immunomodulation by IFNG. Interestingly, IFNG exposure of macrophages induces an increase in intracellular calcium levels that is dependent on HMOX1 generated CO...
February 19, 2018: Autophagy
https://www.readbyqxmd.com/read/29407753/schisandrin-c-enhances-odontoblastic-differentiation-through-autophagy-and-mitochondrial-biogenesis-in-human-dental-pulp-cells
#7
Jyoti Shrestha Takanche, Jeong-Seok Kim, Ji-Eun Kim, S-H Han, Ho-Keun Yi
OBJECTIVE: To investigate the role of Schisandrin C in odontoblastic differentiation, and its relations between autophagy and mitochondrial biogenesis in human dental pulp cells (HPDCs). DESIGN: Fresh third molars were used, and cultured for HDPCs. Western blotting technique, Alizarin red S staining, alkaline phosphatase (ALP) activity, and confocal microscopy were used to detect autophagy, mitochondrial biogenesis, and odontoblastic differentiation. To understand the mechanism of Schisandrin C, the HDPCs were treated with lipopolysaccharide (LPS), autophagy and heme oxygenase-1 (HO-1) inhibitors: 3-Methyladenine (3-MA) and Zinc protoporphyrin IX (ZnPP), respectively...
April 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29344260/dr2-blocker-thioridazine-a-promising-drug-for-ovarian-cancer-therapy
#8
Min Yong, Tinghe Yu, Si Tian, Shuaibin Liu, Jiao Xu, Jianguo Hu, Lina Hu
Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment strategy for ovarian cancer. Thioridazine, a DR2 blocker, has antineoplastic activity in a variety of cancer cells. In view of the requirement for novel therapeutic agents in ovarian cancer, the present study aimed to determine the potential effects of thioridazine in vitro and in vivo. It was revealed that the DR2 blocker thioridazine induced cell death in a dose-dependent manner in ovarian cancer cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29336118/resveratrol-potently-counteracts-quercetin-starvation-induced-autophagy-and-sensitizes-hepg2-cancer-cells-to-apoptosis
#9
Sarah Tomas-Hernández, Jordi Blanco, Cristina Rojas, Joel Roca-Martínez, María José Ojeda-Montes, Raúl Beltrán-Debón, Santiago Garcia-Vallvé, Gerard Pujadas, Lluís Arola, Miquel Mulero
SCOPE: Resveratrol (RSV) has been described as a potent antioxidant, antisteatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory, and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we test the combined effect of QCT and RSV on the autophagy process in HepG2 cells. METHODS AND RESULTS: Autophagy is studied by western blotting, real-time RT-PCR, and cellular staining...
March 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29260265/schisandrin-c-enhances-mitochondrial-biogenesis-and-autophagy-in-c2c12-skeletal-muscle-cells-potential-involvement-of-anti-oxidative-mechanisms
#10
Jeong-Seok Kim, Ho-Keun Yi
The molecular study of muscles is needed to overcome chronic inflammation and maintenance of muscles in the human body. Schisandrin C is a pharmacological compound derived from the fruit of Schisandra chinensis and has many characteristics including anti-inflammation, anti-tumor, and anti-oxidation. However, the cellular and molecular mechanisms of Schisandrin C are still not well understood especially in skeletal muscle. Therefore, the present study was evaluated whether the properties of Schisandrin C in C2C12 skeletal muscle cells involved maintenance of cellular homeostasis and protection against oxidative damage...
February 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29241092/trehalose-protects-against-oxidative-stress-by-regulating-the-keap1-nrf2-and-autophagy-pathways
#11
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...
May 2018: Redox Biology
https://www.readbyqxmd.com/read/29235250/discovery-and-mechanistic-elucidation-of-a-class-of-protein-disulfide-isomerase-inhibitors-for-the-treatment-of-glioblastoma
#12
Anahita Kyani, Shuzo Tamura, Suhui Yang, Andrea Shergalis, Soma Samanta, 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...
January 22, 2018: 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
#13
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
#14
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 (20 hours) cold storage, as well as to analyze the requirement for SIRT1 in autophagy regulation by HO-1...
May 2018: 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
#15
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...
December 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
#16
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 H2 O2 -induced damage in human neuronblastoma SH-SY5Y cells...
January 2018: 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
#17
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
#18
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...
February 2018: 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
#19
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
#20
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
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