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https://www.readbyqxmd.com/read/29321137/novel-function-of-ceramide-for-regulation-of-mitochondrial-atp-release-in-astrocytes
#1
Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D Spassieva, Erhard Bieberich
We reported that amyloid beta peptide (Abeta42) activated neutral sphingomyelinase 2 (nSMase2) thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Abeta42 induced mitochondrial fragmentation in wild type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with Fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria...
January 10, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29279396/protonation-state-of-glutamate-73-regulates-the-formation-of-a-specific-dimeric-association-of-mvdac1
#2
Lucie A Bergdoll, Michael T Lerch, John W Patrick, Kendrick Belardo, Christian Altenbach, Paola Bisignano, Arthur Laganowsky, Michael Grabe, Wayne L Hubbell, Jeff Abramson
The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane and constitutes the primary pathway for the exchange of ions and metabolites between the cytosol and the mitochondria. There is accumulating evidence supporting VDAC's role in mitochondrial metabolic regulation and apoptosis, where VDAC oligomerization has been implicated with these processes. Herein, we report a specific pH-dependent dimerization of murine VDAC1 (mVDAC1) identified by double electron-electron resonance and native mass spectrometry...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229420/ros-mediated-oligomerization-of-vdac2-is-associated-with-quinocetone-induced-apoptotic-cell-death
#3
Xiayun Yang, Shusheng Tang, Daowen Li, Bin Li, Xilong Xiao
Quinocetone (QCT) has been approved and widely used as an animal feed additive in China since 2003. However, investigations indicate that QCT shows potential toxicity both in vitro and in vivo. Although voltage dependent anion channel 1 (VDAC1) involved in regulating QCT-induced apoptotic cell death has been established, the role of voltage dependent anion channel 2 (VDAC2) in QCT-induced toxicity remains unclear. In this study, we showed that QCT-induced cell death was coupled to VDAC2 oligomerization. Moreover, VDAC inhibitor 4, 4'-diisothiocyano stilbene-2, 2'-disulfonic acid (DIDS) alleviated QCT-induced cell death and VDAC2 oligomerization...
December 8, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29196874/upregulation-of-spinal-voltage-dependent-anion-channel-1-contributes-to-bone-cancer-pain-hypersensitivity-in-rats
#4
Xiangpeng Kong, Jinrong Wei, Diyu Wang, Xiaoju Zhu, Youlang Zhou, Shusheng Wang, Guang-Yin Xu, Guo-Qin Jiang
Voltage-dependent anion channel 1 (VDAC1) is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the expression of VDAC1 was upregulated in the L2-5 segments of the spinal dorsal horn at 2 and 3 weeks after injection of tumor cells into the tibial cavity. Intrathecal injection of a VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the over-expression of Toll-like receptor 4 (TLR4)...
December 1, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29185755/vdac1-and-serca3-mediates-progesterone-triggerd-ca2-signaling-in-breast-cancer-cells
#5
Juberiya M Azeez, Vini Ravindran, Viji Remadevi, Arun Surendran, Abdul Jaleel, T R Santhosh Kumar, Sreeja Sreeharshan
Progesterone is a biphasic hormone whose response in breast cancer cells, consisting of an initial proliferative burst, followed by sustained growth arrest. Recently we reported that progesterone induces a time and concentration dependent release of reactive oxygen species and thus regulates the anti-proliferative activity in breast cancer cell line. Furthermore binding of progesterone on progesterone receptor B may regulate the expression of cell cycle control protein p27 and leads to anti proliferative signaling via multiple signaling pathways including p53, PTEN and antioxidant systems...
November 29, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29172540/discovery-of-a-small-molecule-bromodomain-containing-protein-4-brd4-inhibitor-that-induces-amp-activated-protein-kinase-modulated-autophagy-associated-cell-death-in-breast-cancer
#6
Liang Ouyang, Lan Zhang, Jie Liu, Leilei Fu, Dahong Yao, Yuqian Zhao, Shouyue Zhang, Guan Wang, Gu He, Bo Liu
Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that several autophagy-related proteins such as AMP-activated protein kinase (AMPK) were remarkably downregulated in breast cancer. Combined with coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK. After analyses of the pharmacophore and WPF interaction optimization, we designed a small-molecule inhibitor of BRD4, 9f (FL-411) which was validated by cocrystal structure with BD1 of BRD4. Subsequently, 9f was discovered to induce ATG5-dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction and thus activating AMPK-mTOR-ULK1-modulated autophagic pathway in breast cancer cells...
December 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29116138/vascular-endothelial-growth-factor-signaling-requires-glycine-to-promote-angiogenesis
#7
Dongqing Guo, Colin E Murdoch, Hao Xu, Hui Shi, Dayue Darrel Duan, Asif Ahmed, Yuchun Gu
Peripheral vascular occlusive disease (PVOD) is a common manifestation of atherosclerosis, and it has a high rate of morbidity. Therapeutic angiogenesis would re-establish blood perfusion and rescue ischemic tissue. Vascular endothelial growth factor (VEGF) induces angiogenesis and can potentially be used to treat ischemic diseases, yet in clinical trials VEGF has not fulfilled its full potential with side effects. Whether amino acids promote angiogenesis and the molecular mechanisms are largely unknown. Here we showed that (1) Glycine significantly promoted angiogenesis both in vitro and in vivo and effectively protected mitochondrial function...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29104640/penehyclidine-hydrochloride-post-conditioning-reduces-ischemia-reperfusion-induced-cardiomyocyte-apoptosis-in-rats
#8
Hongbao Tan, Li Chen, Jun Ma
Ischemic heart disease is a major cause of mortality and disability worldwide. Timely reperfusion is currently the most effective method of treating ischemic heart disease; however, abrupt reperfusion may cause ischemia/reperfusion (I/R) injury. Apoptosis serves an important role in the progression of myocardial I/R injury and it has been demonstrated that the mitochondria are the center of regulation for apoptosis. Penehyclidine hydrochloride (PHC) is used during surgery and has recently been identified as a new type of anticholinergic drug...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29038520/decrypting-strong-and-weak-single-walled-carbon-nanotubes-interactions-with-mitochondrial-voltage-dependent-anion-channels-using-molecular-docking-and-perturbation-theory
#9
Michael González-Durruthy, Adriano V Werhli, Vinicius Seus, Karina S Machado, Alejandro Pazos, Cristian R Munteanu, Humberto González-Díaz, José M Monserrat
The current molecular docking study provided the Free Energy of Binding (FEB) for the interaction (nanotoxicity) between VDAC mitochondrial channels of three species (VDAC1-Mus musculus, VDAC1-Homo sapiens, VDAC2-Danio rerio) with SWCNT-H, SWCNT-OH, SWCNT-COOH carbon nanotubes. The general results showed that the FEB values were statistically more negative (p < 0.05) in the following order: (SWCNT-VDAC2-Danio rerio) > (SWCNT-VDAC1-Mus musculus) > (SWCNT-VDAC1-Homo sapiens) > (ATP-VDAC)...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29028058/protein-protein-interaction-networks-as-a-new-perspective-to-evaluate-distinct-functional-roles-of-voltage-dependent-anion-channel-isoforms
#10
REVIEW
Marianna Caterino, Margherita Ruoppolo, Annalisa Mandola, Michele Costanzo, Stefania Orrù, Esther Imperlini
Voltage-dependent anion channels (VDACs) are a family of three mitochondrial porins and the most abundant integral membrane proteins of the mitochondrial outer membrane (MOM). VDACs are known to be involved in metabolite/ion transport across the MOM and in many cellular processes ranging from mitochondria-mediated apoptosis to the control of energy metabolism, by interacting with cytosolic, mitochondrial and cytoskeletal proteins and other membrane channels. Despite redundancy and compensatory mechanisms among VDAC isoforms, they display not only different channel properties and protein expression levels, but also distinct protein partners...
November 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29021705/global-analysis-of-ginsenoside-rg1-protective-effects-in-%C3%AE-amyloid-treated-neuronal-cells
#11
Ji Seon Shim, Min-Young Song, Sung-Vin Yim, Seung-Eun Lee, Kang-Sik Park
BACKGROUND: A number of reports have described the protective effects of ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective mechanisms of Rg1 in AD remain elusive. METHODS: To investigate the potential mechanisms of Rg1 in β-amyloid peptide-treated SH-SY5Y cells, a comparative proteomic analysis was performed using stable isotope labeling with amino acids in cell culture combined with nano-LC-MS/MS. RESULTS: We identified a total of 1,149 proteins in three independent experiments...
October 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28980434/mitochondrial-vdac2-and-cell-homeostasis-highlighting-hidden-structural-features-and-unique-functionalities
#12
Svetlana Rajkumar Maurya, Radhakrishnan Mahalakshmi
Voltage-dependent anion channels (VDACs) are the gateway to mitochondrial processes, interlinking the cytosolic and mitochondrial compartments. The mitochondrion acts as a storehouse for cytochrome c, the effector of apoptosis, and hence VDACs become intricately involved in the apoptotic pathway. Isoform 1 of VDAC is abundant in the outer mitochondrial membrane of many cell types, while isoform 2 is the preferred channel in specialized cells including brain and some cancer cells. The primary role of VDACs is metabolite flux...
November 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28954307/in-vitro-effects-of-the-specific-mitochondrial-tspo-ligand-ro5-4864-in-cultured-human-osteoblasts
#13
Rosenberg Nahum, Rosenberg Orit, Weizman Abraham, Veenman Leo, Gavish Moshe
The 18 kDa mitochondrial translocator protein (TSPO) ligands (10 µM), e. g., protoporphyrin IX, PK 11195 and FGIN-1-27, have different effects on metabolism and protein expression in human osteoblasts. In this study, we investigated the archetypical TSPO specific ligand Ro5-4864 (10 µM) effect in primary osteoblasts in culture aiming to further understand the TSPO role in these mature metabolically active cells.We found that following exposure to Ro5-4864, cellular [(18)F]-FDG incorporation and ATP content were reduced by 48% (p<0...
September 27, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28923347/sulforaphane-improves-disrupted-er-mitochondria-interactions-and-suppresses-exaggerated-hepatic-glucose-production
#14
Emily Tubbs, Annika S Axelsson, Guillaume Vial, Claes B Wollheim, Jennifer Rieusset, Anders H Rosengren
AIMS: Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for hepatic metabolism. We wanted to investigate whether SFN could affect hepatic glucose production and MAMs...
September 18, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28918503/coq0-induced-mitochondrial-ptp-opening-triggers-apoptosis-via-ros-mediated-vdac1-upregulation-in-hl-60-leukemia-cells-and-suppresses-tumor-growth-in-athymic-nude-mice-xenografted-nude-mice
#15
You-Cheng Hseu, Varadharajan Thiyagarajan, Ting-Tsz Ou, Hsin-Ling Yang
Coenzyme Q (CoQ) analogs with variable numbers of isoprenoid units have been demonstrated as anticancer and antioxidant/pro-oxidant molecules. This study examined the in vitro and in vivo antitumor and apoptosis activities of CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero isoprenoid side-chains) through upregulation of the Voltage-dependent anion channel 1 (VDAC1) signaling pathway on human promyelocytic leukemia. CoQ0 (0-40 μg/mL) treatment significantly reduced HL-60 cell viability, and up-regulated mitochondrial VDAC1 expression...
September 16, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28918049/silencing-vdac1-expression-by-sirna-inhibits-cancer-cell-proliferation-and-tumor-growth-in%C3%A2-vivo
#16
Tasleem Arif, Lilia Vasilkovsky, Yael Refaely, Alexander Konson, Varda Shoshan-Barmatz
No abstract text is available yet for this article.
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28901260/vdac1-mediated-anticancer-activity-of-gallic-acid-in-human-lung-adenocarcinoma-a549-cells
#17
Aikebaier Maimaiti, Amier Aili, Hureshitanmu Kuerban, Xuejun Li
Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied...
September 11, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28736722/alterations-in-antioxidant-system-mitochondrial-biogenesis-and-autophagy-in-preeclamptic-myometrium
#18
Polina A Vishnyakova, Maria A Volodina, Nadezhda V Tarasova, Maria V Marey, Natalya E Kan, Zulfiya S Khodzhaeva, Mikhail Yu Vysokikh, Gennady T Sukhikh
Preeclampsia is a pregnancy complication which causes significant maternal and fetal morbidity and mortality worldwide. Although intensive research has been performed in the last 40 years, the pathology of preeclampsia is still poorly understood. The present work is a comparative study of the myometrium of women with normal pregnancy, and those with late- and early-onset preeclampsia (n = 10 for each group). We observed significant changes in the levels of antioxidant enzymes, markers of mitochondrial biogenesis and autophagy proteins in preeclamptic myometrium...
December 2017: BBA Clinical
https://www.readbyqxmd.com/read/28713289/mitochondrial-vdac1-a-key-gatekeeper-as-potential-therapeutic-target
#19
REVIEW
Amadou K S Camara, YiFan Zhou, Po-Chao Wen, Emad Tajkhorshid, Wai-Meng Kwok
Mitochondria are the key source of ATP that fuels cellular functions, and they are also central in cellular signaling, cell division and apoptosis. Dysfunction of mitochondria has been implicated in a wide range of diseases, including neurodegenerative and cardiac diseases, and various types of cancer. One of the key proteins that regulate mitochondrial function is the voltage-dependent anion channel 1 (VDAC1), the most abundant protein on the outer membrane of mitochondria. VDAC1 is the gatekeeper for the passages of metabolites, nucleotides, and ions; it plays a crucial role in regulating apoptosis due to its interaction with apoptotic and anti-apoptotic proteins, namely members of the Bcl-2 family of proteins and hexokinase...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28712506/vdac1-functions-in-ca2-homeostasis-and-cell-life-and-death-in-health-and-disease
#20
REVIEW
Varda Shoshan-Barmatz, Yakov Krelin, Anna Shteinfer-Kuzmine
In the outer mitochondrial membrane (OMM), the voltage-dependent anion channel 1 (VDAC1) serves as a mitochondrial gatekeeper, controlling the metabolic and energy cross-talk between mitochondria and the rest of the cell. VDAC1 also functions in cellular Ca2+ homeostasis by transporting Ca2+ in and out of mitochondria. VDAC1 has also been recognized as a key protein in mitochondria-mediated apoptosis, contributing to the release of apoptotic proteins located in the inter-membranal space (IMS) and regulating apoptosis via association with pro- and anti-apoptotic members of the Bcl-2 family of proteins and hexokinase...
June 23, 2017: Cell Calcium
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