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https://www.readbyqxmd.com/read/29149594/conversion-of-bim-bh3-from-activator-to-inhibitor-of-bak-through-structure-based-design
#1
Jason M Brouwer, Ping Lan, Angus D Cowan, Jonathan P Bernardini, Richard W Birkinshaw, Mark F van Delft, Brad E Sleebs, Adeline Y Robin, Ahmad Wardak, Iris K Tan, Boris Reljic, Erinna F Lee, W Douglas Fairlie, Melissa J Call, Brian J Smith, Grant Dewson, Guillaume Lessene, Peter M Colman, Peter E Czabotar
Certain BH3-only proteins transiently bind and activate Bak and Bax, initiating their oligomerization and the permeabilization of the mitochondrial outer membrane, a pivotal step in the mitochondrial pathway to apoptosis. Here we describe the first crystal structures of an activator BH3 peptide bound to Bak and illustrate their use in the design of BH3 derivatives capable of inhibiting human Bak on mitochondria. These BH3 derivatives compete for the activation site at the canonical groove, are the first engineered inhibitors of Bak activation, and support the role of key conformational transitions associated with Bak activation...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29148970/autophagic-cell-death-is-dependent-on-lysosomal-membrane-permeability-through-bax-and-bak
#2
Jason Karch, Tobias G Schips, Bryan D Maliken, Matthew J Brody, Michelle A Sargent, Onur Kanisciak, Jeffery D Molkentin
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and in a previous eLIFE paper, Karch et al., 2013 showed that these 2 effectors are also needed for mitochondrial-dependent cellular necrosis. Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29147465/myricetin-possesses-potential-protective-effects-on-diabetic-cardiomyopathy-through-inhibiting-i%C3%AE%C2%BAb%C3%AE-nf%C3%AE%C2%BAb-and-enhancing-nrf2-ho-1
#3
Hai-Han Liao, Jin-Xiu Zhu, Hong Feng, Jian Ni, Nan Zhang, Si Chen, Huang-Jun Liu, Zheng Yang, Wei Deng, Qi-Zhu Tang
Diabetic cardiomyopathy (DCM) is associated with a greater risk of mortality in patients with diabetes mellitus. Currently, no specific treatment has been suggested for DCM treatment. This study demonstrated that myricetin (M) attenuated DCM-associated cardiac injury in mice subjected to streptozotocin (SZT) and in neonatal rat cardiomyocytes (NRCM) challenged with high glucose. In vivo investigation demonstrated 6 months of M treatment (200 mg/kg/d) significantly alleviated cardiac hypertrophy, apoptosis, and interstitial fibrosis...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29146879/2-cl-mgv-1-ameliorates-apoptosis-in-the-thalamus-and-hippocampus-and-cognitive-deficits-after-cortical-infarct-in-rats
#4
Yicong Chen, Leo Veenman, Sukhdev Singh, Fubing Ouyang, Jiahui Liang, Weixian Huang, Ilan Marek, Jinsheng Zeng, Moshe Gavish
BACKGROUND AND PURPOSE: Focal cortical infarction causes neuronal apoptosis in the ipsilateral nonischemic thalamus and hippocampus, which is potentially associated with poststroke cognitive deficits. TSPO (translocator protein) is critical in regulating mitochondrial apoptosis pathways. We examined the effects of the novel TSPO ligand 2-(2-chlorophenyl)quinazolin-4-yl dimethylcarbamate (2-Cl-MGV-1) on poststroke cognitive deficits, neuronal mitochondrial apoptosis, and secondary damage in the ipsilateral thalamus and hippocampus after cortical infarction...
November 16, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29145424/levosimendan-protects-human-hepatocytes-from-ischemia-reperfusion-injury
#5
Stefanie N Brunner, Nicolai V Bogert, Andreas A Schnitzbauer, Eva Juengel, Anton Moritz, Isabella Werner, Angela Kornberger, Andres Beiras-Fernandez
BACKGROUND: Ischemia-reperfusion injury (IRI) is a major challenge in liver transplantation. The mitochondrial pathway plays a pivotal role in hepatic IRI. Levosimendan, a calcium channel sensitizer, was shown to attenuate apoptosis after IRI in animal livers. The aim of this study was to investigate the effect of levosimendan on apoptosis in human hepatocytes. METHODS: Primary human hepatocytes were either exposed to hypoxia or cultured under normoxic conditions...
2017: PloS One
https://www.readbyqxmd.com/read/29145236/protection-by-nitrite-against-the-ischemic-effects-induced-by-acute-myocardial-infarction-in-mice
#6
Yafei Wang, Xin Song, Xia Yue, Hong Su, Yuanliang Gu, Linda Bowman, Min Ding, Baobo Zou, Jinshun Zhao, Xialu Lin
OBJECTIVE: This research was aimed to investigate the correct dose of nitrite that would act as a protection against the ischemic effects induced by acute myocardial infarction (AMI). METHODS: Mice were randomly divided into a sham-operation group (sham), an AMI operation group (AMI), and a nitrite pretreatment+AMI operation group (N+AMI). Seven days before the AMI operation, mice in the N+AMI group were pretreated with sodium nitrite in drinking water. RESULTS: One week after the AMI operation, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities in both AMI and N+AMI group were significantly higher than those in the sham group, but there were no significant differences between AMI and N+AMI mice...
November 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29144200/mechanisms-underlying-melatonin-mediated-prevention-of-fenvalerate-induced-behavioral-and-oxidative-toxicity-in-zebrafish
#7
Jingjing Han, Cheng Ji, Yichen Guo, Rui Yan, Ting Hong, Yuanyan Dou, Yan An, Shasha Tao, Fenju Qin, Jihua Nie, Chen Ji, Han Wang, Jian Tong, Wei Xiao, Jie Zhang
The neurotoxic effects attributed to the pesticide fenvalerate (FEN) are well-established. The aim of this study was to determine whether melatonin (MLT) was able to protect against FEN-induced behavior, oxidative stress, apoptosis, and neurogenesis using zebrafish (Danio rerio) model. Zebrafish exposed to 100 μg/L FEN for 120 h exhibited decreased swimming activity accompanied by downregulated expression of neurogenesis-related genes (Dlx2, Shha, Ngn1, Elavl3, and Gfap), suggesting that neurogenesis were impaired...
November 16, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/29144199/effect-of-high-hydrostatic-pressure-applied-before-cryopreservation-on-the-survival-rate-and-quality-of-porcine-mesenchymal-stem-cells-after-thawing
#8
Joanna Romanek, Jolanta Opiela, Daniel Lipiński, Zdzisław Smorąg
The aim of the present study was to examine the effects of varied high hydrostatic pressure (HHP) values on survival rate, proliferation rate, cell multipotency (transcript expression of SOX2, C-MYC, and REX1) and apoptosis (expression of phosphatidylserine (PS), SURVIVIN at the RNA level and BAX at the protein level) of porcine mesenchymal stem cells (MSCs). MSCs were isolated from porcine bone marrow and cultured in vitro. Before cryopreservation and storage in liquid nitrogen, MSCs were subjected to HHP at the varied pressures of 20, 30, 40, 50, or 60 MPa for 1 h at 24°C...
November 16, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/29143998/oxytocin-mediates-the-beneficial-effects-of-the-exercise-training-on-breast-cancer
#9
Ali Mohammad Alizadeh, Zahra Heydari, Mostafa Rahimi, Behzad Bazgir, Hossein Shirvani, Sadaf Alipour, Yassaman Heidarian, Solmaz Khalighfard, Amin Isanejad
Exercise training can affect the breast tumor growth. We hypothesized that exercise training may reduce breast tumor growth by inducing Oxytocin (OT) secretion and its related signaling pathways such as PI3K/AKT and ERK. Therefore fifty-six BALB/c mice were equally divided into seven groups to study the effects of OT and atosiban (an oxytocin receptor antagonist) together with the interval exercise training on breast tumor growth, as well as tumor related signaling pathways including PI3K/AKT and ERK. Animal weight, OT plasma level, tumor weight and volume measured at the end of study...
November 16, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29143969/the-molecular-basis-of-cytotoxicity-of-%C3%AE-spinasterol-from-ganoderma-resinaceum-induction-of-apoptosis-and-overexpression-of-p53-in-breast-and-ovarian-cancer-cell-lines
#10
Nada K Sedky, Zaynab El Gammal, Amir E Wahba, Eman Mosad, Zahraa Y Waly, Amira Ali El-Fallal, Reem K Arafa, Nagwa El-Badri
OBJECTIVES: Despite advances in therapy of breast and ovarian cancers, they still remain among the most imperative causes of cancer death in women. The first can be considered one of the most widespread diseases among females, while the latter is more lethal and needs prompt treatment. Thus, the research field can still benefit from discovery of new compounds that can be of potential use in management of these grave illnesses. We hereby aimed to assess the antitumor activity of the phytosterol α-spinasterol isolated from Ganoderma resinaceum mushroom on human breast cancer cell lines (MCF-7, MDA-MB-231), as well as, on human ovarian cancer cell line (SKOV-3)...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29143351/apoptotic-and-antiproliferative-properties-of-3%C3%AE-hydroxy-%C3%AE-5-steroidal-congeners-from-a-partially-purified-column-fraction-of-dendronephthya-gigantea-against-hl-60-and-mcf-7-cancer-cells
#11
I P Shanura Fernando, K K Asanka Sanjeewa, Hyun-Soo Kim, Lei Wang, Won Woo Lee, You-Jin Jeon
Organisms belonging to the genus Dendronephthya are among a group of marine invertebrates that produce a variety of terpenoids with biofunctional properties. Many of these terpenoids have been proven effective as anticancer drugs. Here, we report the antiproliferative effect of 3β-hydroxy-Δ5-steroidal congeners against the proliferation of HL-60 human leukemia cells and MCF-7 human breast cancer cells. The sterol-rich fraction (DGEHF2-1) inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 13...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29142607/curcumin-inhibits-mcf-7-cells-by-modulating-the-nf-%C3%AE%C2%BAb-signaling-pathway
#12
Jun-Li Liu, Yan-Yan Pan, Ou Chen, Yun Luan, Xia Xue, Jing-Jie Zhao, Ling Liu, Hong-Ying Jia
The present study investigated the inhibitory effect of curcumin on human breast cancer MCF-7 cells and investigated the potential underlying molecular mechanisms. MCF-7 cells were cultured with curcumin at different concentrations and time points. The effects of curcumin treatment on breast cancer cell proliferation were studied using a MTT assay. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to assess the mRNA and protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax), nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB) and inhibitor of NF-κB-α (IκBα)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142391/acacia-catechu-ethanolic-seed-extract-triggers-apoptosis-of-scc-25-cells
#13
Thangavelu Lakshmi, Devaraj Ezhilarasan, Upendra Nagaich, Rajagopal Vijayaragavan
Background: Acacia catechu Willd (Fabaceae), commonly known as catechu, cachou, and black cutch, has been studied for its hepatoprotective, antipyretic, antidiarrheal, hypoglycemic, anti-inflammatory, immunomodulatory, antinociceptive, antimicrobial, free radical scavenging, and antioxidant activities. Objective: We evaluated the cytotoxic activity of ethanol extract of A. catechu seed (ACS) against SCC-25 human oral squamous carcinoma cell line. Methods: Cytotoxic effect of ACS extract was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, using concentrations of 0...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142264/impairment-of-bkca-channels-in-human-placental-chorionic-plate-arteries-is-potentially-relevant-to-the-development-of-preeclampsia
#14
Mengzhou He, Fanfan Li, Meitao Yang, Yao Fan, Rajluxmee Beejadhursing, Yin Xie, Yuan Zhou, Dongrui Deng
Preeclampsia has known associations with insufficient placental perfusion. The large-conductance Ca(2+)-activated K(+) (BKca) channels that have recently been found to play important roles in cellular growth and vasodilatation could potentially participate in the development of preeclampsia. However, the mechanisms by which downregulated BKca channels are involved in the development of preeclampsia remain unknown. In this study, we investigated the mechanism(s) underlying the impairment of vascular tone regulation by BKca channels in human placental chorionic plate arteries (CPAs) in preeclampsia...
November 16, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29141547/cardioprotective-effects-of-serca2a-overexpression-against-ischemia-reperfusion-induced-injuries-in-rats
#15
Yan Jian, Li-Li Tian, Lin-Hui Wang, Xiao-Dong Zhao, Jing-Wei Chen, Koji Murao, Wei Zhu, Liang Dong, Guo-Qing Wang, Wan-Ping Sun, Guo-Xing Zhang
AIMS: The aim of the present study is to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after ischemia/reperfusion (I/R) exposure and the related mechanisms involved. METHODS AND RESULTS: Rats were subjected to left anterior descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats (Serca2aTG) rats compared to wild type (WT) rats...
November 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29141514/regulatory-effect-of-neuroglobin-in-the-recovery-of-spinal-cord-injury
#16
Ji-Lin Dai, Yun Lin, Yong-Jian Yuan, Shi-Tong Xing, Yi Xu, Qiang-Hua Zhang, Ji-Kang Min
OBJECTIVE: The present study was aimed to investigate the therapeutic potential of neuroglobin in the recovery of spinal cord injury. METHODS: The male albino Wistar strain rats were used as an experimental model, and adeno associated virus (AAV) was administered in the T12 section of spinal cord ten days prior to the injury. Basso Beattie Bresnahan (BBB) locomotor rating scale was used to determine the recovery of the hind limb during four weeks post-operation...
November 16, 2017: Journal of Spinal Cord Medicine
https://www.readbyqxmd.com/read/29141388/-effects-of-smp-30-overexpression-on-apoptosis-of-human-lens-epithelial-cells-induced-by-ultraviolet-b-irradiation
#17
H Teng, L Y Huang, F Tian, L J Dong, H Zhang
Objective: This study was to observe the effect of SMP-30 on ultraviolet B (UVB)-induced apoptosis of human lens epithelial cells(HLE-B3) in vitro. Methods: Experimental study. The SMP-30 cDNA was amplified by PCR and inserted into the pRFP-N1 expressing vector which had been double digested by XhoI/HindIII. HLE-B3 cells were cultured and divided into three groups: normal group, pRFP-N1 vector plasmid group and pRFP-N1-SMP-30 plasmid group (SMP-30). Then cells were exposed to UVB and the survival rate of cells was detected by MTT assay...
November 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29141249/%C3%AE-catenin-cooperates-with-creb-binding-protein-to-promote-the-growth-of-tumor-cells
#18
Wendan Yu, Liren Li, Fufu Zheng, Wenjing Yang, Shilei Zhao, Chunfang Tian, Wenwen Yin, Yiming Chen, Wei Guo, Lijuan Zou, Wuguo Deng
BACKGROUND/AIMS: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. METHODS: We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29141243/trolline-ameliorates-liver-fibrosis-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway-promoting-hsc-apoptosis-and-suppressing-autophagy
#19
Facheng Bai, Quanfang Huang, Jinlan Nie, Shengjuan Lu, Chunyuan Lu, Xunshuai Zhu, Yuxin Wang, Lang Zhuo, Zhongpeng Lu, Xing Lin
BACKGROUND/AIMS: Previous studies have shown that trolline possesses various forms of pharmacological activity, including antibacterial and antiviral potency. The present paper addressed the putative hepatoprotective effects of trolline. METHODS: Rats received 2 ml/kg CCl4 (mixed 1: 1 in peanut oil) intragastrically twice a week for 8 weeks to induce hepatic fibrosis. The animals were then treated with trolline for additional 4 weeks. Liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29141222/jnk-promotes-epithelial-cell-anoikis-by-transcriptional-and-post-translational-regulation-of-bh3-only-proteins
#20
Nomeda Girnius, Roger J Davis
Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis). While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK) signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo...
November 14, 2017: Cell Reports
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