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https://www.readbyqxmd.com/read/29155130/dibromoacetic-acid-induced-cl-ly1-2-9-t-cell-apoptosis-and-activation-of-mapks-signaling-cascades
#1
Xiao-Rong Zhou, Wen-Bo Jiang, Yang-Ting Zhang, Ting-Ting Gong, Shu-Ying Gao
Dibromoacetic acid (DBA), a haloacetic acid by-product of disinfection of drinking water, can cause many adverse effects in test animals, including immunotoxicity. However, the underlying molecular mechanism for the immunomodulatory effects remains unclear. The present study was undertaken to help in defining some potential mechanisms for this type of toxicity. Here, Cl.Ly1+2/-9 T-cells were exposed to varying levels of DBA and then several parameters, including cell survival, apoptosis, changes in mitochondrial potentials, and effects on select kinases (i...
November 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29154799/integrative-omics-data-analyses-of-repeated-dose-toxicity-of-valproic-acid-in-vitro-reveal-new-mechanisms-of-steatosis-induction
#2
Simone G J van Breda, Sandra M H Claessen, Marcel van Herwijnen, Daniël H J Theunissen, Danyel G J Jennen, Theo M C M de Kok, Jos C S Kleinjans
Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug probably by its HDAC inhibiting properties, which may cause steatosis in the liver. The present study investigates the effect of repetitive VPA treatment of primary human hepatocytes (PHH) on whole genome gene expression-, DNA methylation-, and miRNA changes, using microarrays and integrated data analyses. PHH were exposed to a non-cytotoxic dose of VPA for 5days daily which induced lipid accumulation. Part of the PHH was left untreated for 3days for studying the persistence of 'omics' changes...
November 14, 2017: Toxicology
https://www.readbyqxmd.com/read/29152653/elaidic-acid-induces-cell-apoptosis-through-induction-of-ros-accumulation-and-endoplasmic-reticulum-stress-in-sh%C3%A2-sy5y-cells
#3
Wei-Wei Ma, Lei Zhao, Lin-Hong Yuan, Huan-Ling Yu, Hui Wang, Xin-Yuan Gong, Feng Wei, Rong Xiao
Elaidic acid, which is a major trans fatty acid, has been reported to be involved in neurotoxicity; however, the underlying molecular mechanisms underlying its neurotoxic effects remain largely unknown. Therefore, the present study aimed to investigate the potential mechanisms underlying elaidic acid‑induced neuronal damage in vitro. The SH‑SY5Y neuroblastoma cell line was used as a model in the present study. Following treatment of cells with various concentrations of elaidic acid or with vehicle for 24 h, cell viability was measured using the MTT assay...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29152251/oxygen-the-forgotten-nutrient
#4
Paul Trayhurn
O2 is essential for the maintenance and growth of aerobic animals, similar to the essentiality of what are classically considered nutrients. Nevertheless, O2 is not customarily regarded as a nutrient, this reflecting the route by which it enters the body - through the lungs or gills in vertebrates, rather than via the mouth and gastrointestinal tract. A relative deficiency of O2 occurs at high altitudes and during deep-sea diving, to which distinct adaptations occur. Deficiency is also evident in lung diseases such as emphysema...
2017: Journal of Nutritional Science
https://www.readbyqxmd.com/read/29150527/transcriptional-regulators-of-redox-balance-and-other-homeostatic-processes-with-the-potential-to-alter-neurodegenerative-disease-trajectory
#5
REVIEW
Scott W Burnside, Giles E Hardingham
Diverse neurodegenerative diseases share some common aspects to their pathology, with many showing evidence of disruption to the brain's numerous homeostatic processes. As such, imbalanced inflammatory status, glutamate dyshomeostasis, hypometabolism and oxidative stress are implicated in many disorders. That these pathological processes can influence each other both up- and downstream makes for a complicated picture, but means that successfully targeting one area may have an effect on others. This targeting requires an understanding of the mechanisms by which homeostasis is maintained during health, in order to uncover strategies to boost homeostasis in disease...
November 17, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29149835/forkhead-transcription-factors-formulating-a-foxo-target-for-cognitive-loss
#6
Kenneth Maiese
BACKGROUND: With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. METHODS: Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29149603/structural-basis-of-mitochondrial-transcription-initiation
#7
Hauke S Hillen, Yaroslav I Morozov, Azadeh Sarfallah, Dmitry Temiakov, Patrick Cramer
Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29148840/resveratrol-induces-mitochondrial-apoptosis-and-inhibits-epithelial-mesenchymal-transition-in-oral-squamous-cell-carcinoma-cells
#8
Seong-Eon Kim, Sang-Hun Shin, Jae-Yeol Lee, Chul-Hoon Kim, In-Kyo Chung, Hae-Mi Kang, Hae-Ryoun Park, Bong-Soo Park, In-Ryoung Kim
OSCC is the most common malignant cancer of the head and neck. EMT is an essential cellular process critical to the morphogenesis and homeostasis of solid tissues. It is also involved in the initial stage of cancer metastasis and invasion in which cells lose epithelial characteristics. While cancer therapy protocols such as surgery, radiation, and chemotherapy are effective and useful, the drug tolerance and toxicity of OSCC patients remain a problem. Resveratrol is mainly produced in red grape skin and exhibits anti-oxidative, anti-inflammatory, anti-proliferative, and anti-cancer properties...
November 17, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29148034/role-of-p62-sqstm1-beyond-autophagy-a-lesson-learned-from-drug-induced-toxicity-in-vitro
#9
Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
BACKGROUND AND PURPOSE: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood...
November 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29147009/mitochondrial-uqcrb-as-a-new-molecular-prognostic-biomarker-of-human-colorectal-cancer
#10
Hyun-Chul Kim, Junghwa Chang, Hannah S Lee, Ho Jeong Kwon
Ubiquinol cytochrome c reductase binding protein (UQCRB) is important for mitochondrial complex III stability, electron transport, cellular oxygen sensing and angiogenesis. However, its potential as a prognostic marker in colorectal cancer (CRC) remains unclear. The aim of this study was to determine whether UQCRB can be used as a diagnostic molecular marker for CRC. The correlation between the expression of three genes (UQCRB, UQCRFS1 and MT-CYB) in the mitochondrial respiratory chain complex III and clinico-pathological features was determined...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29146687/exercise-induces-muscle-fiber-type-switching-via-transient-receptor-potential-melastatin-2-trpm2-dependent-ca-2-signaling
#11
Seo-Ho Lee, Byung-Ju Kim, Dae-Ryoung Park, Uh-Hyun Kim
The aim of the present study was to examine whether transient receptor potential melastatin 2 (TRPM2) plays a role in muscle fiber type transition during exercise. Mice were trained at a speed of 12 m/min at a slope of 0 ° for 60 min 5 consecutive d/wk for 4-wk. Exhaustion tests were performed on the treadmill (the speed was set at 6 m/min at a slope of 0° and increased at a rate of 1 m/min every 6 min). Isolated primary skeletal muscle cells from TRPM2 knockout (KO) mice showed lower amplitudes of electrical stimuli (ES)-induced Ca(2+) signals when compared to wild-type (WT) mice, due to a defect in Ca(2+) influx...
November 16, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29144408/antioxidant-effect-of-barley-sprout-extract-via-enhancement-of-nuclear-factor-erythroid-2-related-factor-2-activity-and-glutathione-synthesis
#12
Yun-Hee Lee, Sou Hyun Kim, Seunghyun Lee, Kyung-Mi Kim, Jae-Chul Jung, Tae Gen Son, Sung Hwan Ki, Woo-Duck Seo, Jae-Hwan Kwak, Jin Tae Hong, Young-Suk Jung
We previously showed that barley sprout extract (BSE) prevents chronic alcohol intake-induced liver injury in mice. BSE notably inhibited glutathione (GSH) depletion and increased inflammatory responses, revealing its mechanism of preventing alcohol-induced liver injury. In the present study we investigated whether the antioxidant effect of BSE involves enhancing nuclear factor-erythroid 2 related factor 2 (Nrf2) activity and GSH synthesis to inhibit alcohol-induced oxidative liver injury. Mice fed alcohol for four weeks exhibited significantly increased oxidative stress, evidenced by increased malondialdehyde (MDA) level and 4-hydroxynonenal (4-HNE) immunostaining in the liver, whereas treatment with BSE (100 mg/kg) prevented these effects...
November 16, 2017: Nutrients
https://www.readbyqxmd.com/read/29142404/chalepin-a-compound-from-ruta-angustifolia-l-pers-exhibits-cell-cycle-arrest-at-s-phase-suppresses-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathway-signal-transducer-and-activation-of-transcription-3-stat3-phosphorylation-and-extrinsic-apoptotic-pathway-in-non-small-cell
#13
Jaime Stella Moses Richardson, Norhaniza Aminudin, Sri Nurestri Abd Malek
Background: Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. Objective: A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142323/nkx6-1-decline-accompanies-mitochondrial-dna-reduction-but-subtle-nucleoid-size-decrease-in-pancreatic-islet-%C3%AE-cells-of-diabetic-goto-kakizaki-rats
#14
Tomáš Špaček, Vojtěch Pavluch, Lukáš Alán, Nikola Capková, Hana Engstová, Andrea Dlasková, Zuzana Berková, František Saudek, Petr Ježek
Hypertrophic pancreatic islets (PI) of Goto Kakizaki (GK) diabetic rats contain a lower number of β-cells vs. non-diabetic Wistar rat PI. Remaining β-cells contain reduced mitochondrial (mt) DNA per nucleus (copy number), probably due to declining mtDNA replication machinery, decreased mt biogenesis or enhanced mitophagy. We confirmed mtDNA copy number decrease down to <30% in PI of one-year-old GK rats. Studying relations to mt nucleoids sizes, we employed 3D superresolution fluorescent photoactivable localization microscopy (FPALM) with lentivirally transduced Eos conjugate of mt single-stranded-DNA-binding protein (mtSSB) or transcription factor TFAM; or by 3D immunocytochemistry...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141573/liver-protective-effects-of-extra-virgin-olive-oil-interaction-between-its-chemical-composition-and-the-cell-signaling-pathways-involved-in-protection
#15
Sandra A Soto-Alarcon, Rodrigo Valenzuela, Alfonso Valenzuela, Luis A Videla
BACKGROUND AND OBJECTIVE: The liver is an organ susceptible to a multitude of injuries that causes liver damage, like steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Extra virgin olive oil (EVOO), presents several protective effects on the liver, reducing hepatic steatosis, hepatocyte ballooning, fibrogenesis, preventing lipid peroxidation, among other effects. Due to its high levels of monounsaturated fatty acids, mainly oleic acid and phenolic compounds, such as hydroxytyrosol and oleuropein, EVOO is able to participate in the activation of different signaling pathways in the hepatocytes involved in the prevention of inflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and insulin resistance, allowing the prevention or resolution of liver damage...
November 14, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29138850/role-of-mitochondrial-function-in-the-invasiveness-of-human-colon-cancer-cells
#16
Chen-Sung Lin, Li-Tzu Liu, Liang-Hung Ou, Siao-Cian Pan, Chia-I Lin, Yau-Huei Wei
We investigated the role of mitochondrial function in the invasiveness of human colorectal cancer (CRC) cell lines, using paired primary SW480 and metastatic SW620 cells, and appraised the clinical relevance of the alteration of mtDNA copy number in 33 pairs of CRC specimens after surgical resection. Suppression of mitochondrial function was achieved by the exposure of cells to oligomycin A (OA) or by knockdown of mitochondrial transcriptional factor A (TFAM) to evaluate their effects on energy metabolism, reactive oxygen species, protein expression levels of epithelial-mesenchymal transition (EMT) markers and invasive activity of CRC cells...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29138824/genetic-mutational-testing-of-chinese-children-with-familial-hematuria-with-biopsy%C3%A2-proven-fsgs
#17
Yongzhen Li, Ying Wang, Qingnan He, Xiqiang Dang, Yan Cao, Xiaochuan Wu, Shuanghong Mo, Xiaoxie He, Zhuwen Yi
Focal segmental glomerulosclerosis (FSGS) is a pathological lesion rather than a disease, with a diverse etiology. FSGS may result from genetic and non‑genetic factors. FSGS is considered a podocyte disease due to the fact that in the majority of patients with proven‑FSGS, the lesion results from defects in the podocyte structure or function. However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes. Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH)...
November 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29137472/changes-in-transcription-pattern-lead-to-a-marked-decrease-in-cox-cs-and-sqr-activity-after-the-developmental-point-of-the-22-nd-gestational-week
#18
H Kolarova, J Krizova, M Hulkova, H Hansikova, H Hulkova, V Smid, J Zeman, T Honzik, M Tesarova
Tissue differentiation and proliferation throughout fetal development interconnect with changes in the Oxidative Phosphorylation System (OXPHOS) on the cellular level. Reevaluation of the expression data revealed a significant increase in COX4 and MTATP6 liver transcription levels after the 22(nd) gestational week (GW) which inspired us to characterize its functional impact. Specific activities of cytochrome c oxidase (COX), citrate synthase (CS), succinate-coenzyme Q reductase (SQR) and mtDNA determined by spectrophotometry and RT-PCR were studied in a set of 25 liver and 18 skeletal muscle samples at 13(th) to 29(th) GW...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29137431/mitochondrial-dna-depletion-mitochondrial-mutations-and-high-tfam-expression-in-hepatocellular-carcinoma
#19
Lihua Qiao, Guoqing Ru, Zhuochao Mao, Chenghui Wang, Zhipeng Nie, Qiang Li, Yiyi Huang-Yang, Ling Zhu, Xiaoyang Liang, Jialing Yu, Pingping Jiang
We investigated the role of mitochondrial genetic alterations in hepatocellular carcinoma by directly comparing the mitochondrial genomes of 86 matched pairs of HCC and non-tumor liver samples. Substitutions in 637 mtDNA sites were detected, comprising 89.80% transitions and 6.60% transversions. Forty-six somatic variants, including 15 novel mutations, were identified in 40.70% of tumor tissues. Of those, 21 were located in the non-coding region and 25 in the protein-coding region. Twenty-two somatic nonsynonymous changes were identified as putative pathogenic variants, including 4 truncating mutations produced by three frameshifts (MT-ATP6 8628 insC; MT-ND5 13475 T-del, and MT-CYB 14984 insA) and 1 nonsense mutation in MT-CO3 9253 G>A...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29126696/coordination-of-mitochondrial-biogenesis-by-pgc-1%C3%AE-in-human-skeletal-muscle-a-re-evaluation
#20
REVIEW
Hashim Islam, Brittany A Edgett, Brendon J Gurd
The transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1α) is proposed to coordinate skeletal muscle mitochondrial biogenesis through the integrated induction of nuclear- and mitochondrial-encoded gene transcription. This paradigm is based largely on experiments demonstrating PGC-1α's ability to co-activate various nuclear transcription factors that increase the expression of mitochondrial genes, as well PGC-1α's direct interaction with mitochondrial transcription factor A within mitochondria to increase the transcription of mitochondrial DNA...
November 7, 2017: Metabolism: Clinical and Experimental
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