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https://www.readbyqxmd.com/read/29408999/hippocampal-mutant-app-and-amyloid-beta-induced-cognitive-decline-dendritic-spine-loss-defective-autophagy-mitophagy-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#1
Maria Manczak, Ramesh Kandimalla, Xiangling Yin, P Hemachandra Reddy
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in 12-month-old APP transgenic mice. Using rotarod and Morris Water Maze tests, immunoblotting & immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and quantified dendritic spines and mitochondrial number and length in 12-month-old APP mice that express swedish mutation...
February 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29355527/isovitexin-iv-induces-apoptosis-and-autophagy-in-liver-cancer-cells-through-endoplasmic-reticulum-stress
#2
Sheng-Xiang Lv, Xiao Qiao
Liver cancer is a leading cause of cancer death worldwide, and novel chemotherapeutic drugs to suppress liver cancer are urgently required. Isovitexin (IV), a glycosylflavonoid, is extracted from rice hulls of Oryza sativa, and has various biological activities. However, the anti-tumor effect of IV against liver cancer has not yet been demonstrated in vitro or in vivo. In the present study, we showed that IV significantly suppressed the growth of liver cancer cells. Mechanistic studies indicated that IV induced apoptosis by the mitochondrial apoptotic pathway, as evidenced by the increase of Bax, cleaved Caspase-3, poly (ADP-ribose) polymerase (PARP), and cytoplasm Cyto-c released from mitochondria...
January 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29352609/induction-of-mitophagy-in-the-hei-oc1-auditory-cell-line-and-activation-of-the-atg12-lc3-pathway-in-the-organ-of-corti
#3
Cristian Setz, Anne-Sophie Benischke, Anna Catharina Pinho Ferreira Bento, Yves Brand, Soledad Levano, Franziska Paech, Katharina Leitmeyer, Daniel Bodmer
Autophagy is a highly evolutionary conserved quality control defense mechanism within cells, which has also been implicated in cell death processes. In the mammalian inner ear, autophagy has been shown to play a role during early morphogenesis as well as in adult cochlear hair cells exposed to ototoxic insults. Mitophagy, a selective autophagic cell process targeting mitochondria, hasn't been studied in the inner ear so far. On this work, we searched for molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1 (HEI-OC1) cells as well as in the organ of Corti (OC)...
January 11, 2018: Hearing Research
https://www.readbyqxmd.com/read/29352110/melatonin-inhibits-apoptotic-cell-death-induced-by-vibrio-vulnificus-vvha-via-melatonin-receptor-2-coupling-with-ncf-1
#4
Sei-Jung Lee, Hyun Jik Lee, Young Hyun Jung, Jun Sung Kim, Sang Ho Choi, Ho Jae Han
Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial (HCT116) cells induced by the hemolysin (VvhA) produced by V. vulnificus. Melatonin (1 μM) significantly inhibited apoptosis induced by the recombinant protein (r) VvhA, which had been inhibited by the knockdown of MT2...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29289836/brevilin-a-induces-apoptosis-and-autophagy-of-colon-adenocarcinoma-cell-ct26-via-mitochondrial-pathway-and-pi3k-akt-mtor-inactivation
#5
Pengtao You, Hezhen Wu, Meng Deng, Jingling Peng, Fangping Li, Yanfang Yang
Brevilin A is a sesquiterpene lactone isolated from Centipeda minima and possesses inhibitory effects on proliferation of various tumor cells. In this study, Brevilin A inhibitory effect on proliferation and its molecular mechanism of action were investigated both in vivo and in vitro in colon adenocarcinoma CT26 cells. The results indicated that the inhibitory effect of Brevilin A in CT26 proliferation was dose-dependent and this effect was due to apoptosis. Furthermore, Brevilin A increased ROS levels, decreased mitochondrial membrane potential (MMP) and induced apoptosis of CT26 cell in a dose-dependent manner...
December 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29277324/sirtuin-3-induced-macrophage-autophagy-in-regulating-nlrp3-inflammasome-activation
#6
Penghao Liu, Gaojian Huang, Tong Wei, Jing Gao, Chenglin Huang, Mengwei Sun, Limin Zhu, Weili Shen
Defective autophagy of monocytes or macrophages might result in NLRP3 inflammasome activation and cause vascular metabolic inflammation. However, the mechanism underlying the initiation of the autophagy response to hyperlipidaemia remains unclear. Sirtuin 3 (SIRT3), an NAD-dependent deacetylase, is sensitive to the metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated autophagy in regulating NLRP3 inflammasome activation. We determined that the inhibition of autophagy and the activation of the NLRP3 inflammasome were concomitant with reduced SIRT3 levels both in peripheral blood monocytes from obese humans and in palmitate-treated THP-1 cells...
December 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29229994/autophagy-induced-during-apoptosis-degrades-mitochondria-and-inhibits-type-i-interferon-secretion
#7
Lisa M Lindqvist, Daniel Frank, Kate McArthur, Toby A Dite, Michael Lazarou, Jonathan S Oakhill, Benjamin T Kile, David L Vaux
Cells undergoing Bax/Bak-mediated apoptosis exhibit signs of autophagy, but how it is activated and its significance is unknown. By directly activating Bax/Bak with BH3-only proteins or BH3 mimetic compounds, we demonstrate that mitochondrial damage correlated with a rapid increase in intracellular [AMP]/[ATP], phosphorylation of 5' AMP-activated protein kinase (AMPK), and activation of unc-51 like autophagy activating kinase 1 (ULK1). Consequently, autophagic flux was triggered early in the apoptotic pathway, as activation of the apoptosome and caspases were not necessary for its induction...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29222162/dual-inhibition-of-pik3c3-and-fgfr-as-a-new-therapeutic-approach-to-treat-bladder-cancer
#8
Chun-Han Chen, C Changou, Tsung-Han Hsieh, Yu-Ching Lee, Cheng-Ying Chu, Kai-Cheng Hsu, Hao-Ching Wang, Yu-Chen Lin, Yan-Ni Lo, Yun-Ru Liu, Jing-Ping Liou, Yun Yen
PURPOSE: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant anti-bladder cancer activity in vitro and in vivo via promoting autophagy-dependent cell death. Here, we aim to elucidate the underlying mechanisms. EXPERIMENTAL DESIGN: Autophagy flux, morphology and intracellular organelles were evaluated by western blotting, transmission electron microscope and fluorescence microscope. Molecular docking, surface plasmon resonance assay were performed to identify drug-protein interaction...
December 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29203401/skeletal-muscle-from-aged-american-quarter-horses-shows-impairments-in-mitochondrial-biogenesis-and-expression-of-autophagy-markers
#9
Chengcheng Li, Sarah H White, Lori K Warren, Stephanie E Wohlgemuth
Aging is associated with decreased mitochondrial content and function in skeletal muscle, possibly due to compromised biogenesis and autophagic removal of dysfunctional mitochondria. The aim of this study was to compare markers of mitochondrial content and biogenesis and of autophagy between skeletal muscle from young and aged American Quarter Horses. Citrate synthase protein and mtDNA copy number were decreased in triceps brachii (TB) muscle (P<0.05) from aged horses, suggesting an age-related decline in mitochondrial content...
December 1, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29138276/metabolic-reprogramming-ensures-cancer-cell-survival-despite-oncogenic-signaling-blockade
#10
Hui-Wen Lue, Jennifer Podolak, Kevin Kolahi, Larry Cheng, Soumya Rao, Devin Garg, Chang-Hui Xue, Juha K Rantala, Jeffrey W Tyner, Kent L Thornburg, Ann Martinez-Acevedo, Jen-Jane Liu, Christopher L Amling, Charles Truillet, Sharon M Louie, Kimberly E Anderson, Michael J Evans, Valerie B O'Donnell, Daniel K Nomura, Justin M Drake, Anna Ritz, George V Thomas
There is limited knowledge about the metabolic reprogramming induced by cancer therapies and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation...
October 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/29128638/ulk1-regulated-autophagy-a-mechanism-in-cellular-protection-for-aldh2-against-hyperglycemia
#11
Min Liu, Songhe Lu, Wei He, Le Zhang, Ying Ma, Ping Lv, Meijuan Ma, Wenjun Yu, Jiaxing Wang, Mingming Zhang, Yingmei Zhang, Yan Li
Mitochondrial aldehyde dehydrogenase 2 (ALDH2), an important enzyme in the elimination of toxic aldehydes, is involved in cardioprotection against diabetes mellitus. This study was designed to examine the mechanism behind ALDH2-offered protection against high glucose exposure with a focus on autophagy. H9C2 cells were cultured with normal or high glucose medium in the presence or absence of the ALDH2 agonist Alda-1. GFP-LC3 puncta and immunofluorescence were employed to assess autophagosome formation. Western blotting was applied to evaluate autophagy protein markers Atg5, LC3, p62, ULK1 phosphorylation and ALDH2...
November 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29076973/blocking-liver-autophagy-accelerates-apoptosis-and-mitochondrial-injury-in-hepatocytes-and-reduces-time-to-mortality-in-a-murine-sepsis-model
#12
Takehiko Oami, Eizo Watanabe, Masahiko Hatano, Youichi Teratake, Lisa Fujimura, Akemi Sakamoto, Chizuru Ito, Kiyotaka Toshimori, Paul E Swanson, Shigeto Oda
Autophagy plays an important role in cell survival, sequestering and degrading a wide variety of substrates. Although an increase of autophagosomes in liver has been reported in sepsis patients as well as septic mice, the influence of autophagy on liver injury, the interaction between autophagy, and other types of cell death in sepsis remains unclear. The aim of this study was to elucidate the contribution of liver autophagy to the pathophysiology of sepsis. We performed a cecal ligation and puncture (CLP) on liver-specific autophagy-deficient (Alb-Cre/Atg5) mice (six to eight-week-old male)...
October 25, 2017: Shock
https://www.readbyqxmd.com/read/29076434/cjk-7-a-novel-flavonoid-from-paulownia-tomentosa-triggers-cell-death-cascades-in-hct-116-human-colon-carcinoma-cells-via-redox-signaling
#13
Mahendra Pal Singh, Ki Hun Park, Sun Chul Kang
BACKGROUND: Colon cancer is the second most common cancer to cause death worldwide. About half of colon cancer patients require adjuvant therapy to control relapse following surgical resection. Therefore, abolition of tumor cell progression using an effective chemotherapeutic agent holds a feasible approach to treat patients suffering from colon cancer. In the present study, we evaluated the effects of geranylated flavonoid CJK-7, isolated from Paulownia tomentosa on HCT-116 human colon carcinoma cells...
October 26, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29056525/ketogenic-diet-attenuates-neuronal-injury-via-autophagy-and-mitochondrial-pathways-in-pentylenetetrazol-kindled-seizures
#14
Bao-Hui Wang, Qun Hou, Yu-Qiang Lu, Meng-Meng Jia, Tao Qiu, Xiao-Hang Wang, Zheng-Xiang Zhang, Yan Jiang
Autophagy alterations have been observed in a variety of neurological disorders, however, very few studies have focused on autophagy alterations in epilepsy. The ketogenic diet (KD) likely ameliorates neuronal loss in several seizure models. However, whether this neuroprotective function occurs via starvation-induced autophagy and its prevalence in chronic kindled seizures remains unknown. The aim of this study was to determine the role of autophagy following seizure under KD, and the potential mechanism involved...
October 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28965951/polydatin-ameliorates-diabetic-cardiomyopathy-via-sirt3-activation
#15
Mingming Zhang, Shanjie Wang, Zheng Cheng, Zhenyu Xiong, Jianjun Lv, Zhi Yang, Tian Li, Shuai Jiang, Jing Gu, Dongdong Sun, Yanhong Fan
BACKGROUND: Diabetic cardiomyopathy is identified as cardiac ventricular dysfunction induced by an insulin shortage in diabetic patients. Our previous studies have shown that Polydatin (PD) alleviates cardiac dysfunction after myocardial infarction (MI) injury. Nevertheless, the mechanism by which PD regulates diabetic cardiomyopathy has not been reported. METHODS: In this study, we demonstrated the effects and described the mechanisms of PD in diabetic cardiomyopathy in both adult mouse hearts and neonatal mouse cardiomyocytes...
November 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28947954/bh3-mimetic-obatoclax-gx15-070-mediates-mitochondrial-stress-predominantly-via-mcl-1-inhibition-and-induces-autophagy-dependent-necroptosis-in-human-oral-cancer-cells
#16
Prasad Sulkshane, Tanuja Teni
We have previously reported overexpression of antiapoptotic MCL-1 protein in human oral cancers and its association with therapy resistance and poor prognosis, implying it to be a potential therapeutic target. Hence, we investigated the efficacy and mechanism of action of Obatoclax, a BH3 mimetic pan BCL-2 inhibitor in human oral cancer cell lines. All cell lines exhibited high sensitivity to Obatoclax with complete clonogenic inhibition at 200-400 nM concentration which correlated with their MCL-1 expression...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28945807/modulating-lysosomal-function-through-lysosome-membrane-permeabilization-or-autophagy-suppression-restores-sensitivity-to-cisplatin-in-refractory-non-small-cell-lung-cancer-cells
#17
Magdalena Circu, James Cardelli, Martin Barr, Kenneth O'Byrne, Glenn Mills, Hazem El-Osta
Lung cancer is the leading cause of cancer-related deaths. Most patients develop resistance to platinum within several months of treatment. We investigated whether triggering lysosomal membrane permeabilization (LMP) or suppressing autophagy can restore cisplatin susceptibility in lung cancer with acquired chemoresistance. Cisplatin IC50 in A549Pt (parental) and A549cisR (cisplatin resistant) cells was 13 μM and 47 μM, respectively. Following cisplatin exposure, A549cisR cells failed to elicit an apoptotic response...
2017: PloS One
https://www.readbyqxmd.com/read/28841353/esrra-estrogen-related-receptor-alpha-is-a-key-coordinator-of-transcriptional-and-post-translational-activation-of-autophagy-to-promote-innate-host-defense
#18
Soo Yeon Kim, Chul-Su Yang, Hye-Mi Lee, Jin Kyung Kim, Yi-Sak Kim, Ye-Ram Kim, Jae-Sung Kim, Tae Sung Kim, Jae-Min Yuk, Catherine Rosa Dufour, Sang-Hee Lee, Jin-Man Kim, Hueng-Sik Choi, Vincent Giguère, Eun-Kyeong Jo
The orphan nuclear receptor ESSRA (estrogen related receptor, alpha) is a key regulator of energy homeostasis and mitochondrial function. Macroautophagy/autophagy, an intracellular degradation process, is a critical innate effector against intracellular microbes. Here, we demonstrate that ESRRA is required for the activation of autophagy to promote innate antimicrobial defense against mycobacterial infection. AMP-activated protein kinase pathway and SIRT1 (sirtuin 1) activation led to induction of ESRRA, which is essential for autophagosome formation, in bone marrow-derived macrophages...
August 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28825685/the-effects-of-silica-nanoparticles-on-apoptosis-and-autophagy-of-glioblastoma-cell-lines
#19
Rafał Krętowski, Magdalena Kusaczuk, Monika Naumowicz, Joanna Kotyńska, Beata Szynaka, Marzanna Cechowska-Pasko
Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LBC3 and LN-18 cells. It has been demonstrated that SiNPs of 7 nm, 5-15 nm and 10-20 nm induce time- and dose-dependent cytotoxicity in LBC3 and LN-18 cell lines. In contrast to glioblastoma cells, we observed only weak reduction in viability of normal skin fibroblasts treated with SiNPs...
August 21, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#20
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
2017: Cellular Physiology and Biochemistry
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