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Mitochondrial pharmacology

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https://www.readbyqxmd.com/read/28647370/oleanolic-acid-prevents-cartilage-degeneration-in-diabetic-mice-via-ppar%C3%AE-associated-mitochondrial-stabilization
#1
Xia Kang, Zhikui Yang, Jun Sheng, Jin-Biao Liu, Qing-Yun Xie, Wei Zheng, Ken Chen
Hyperglycemia-induced cartilage degeneration induces osteoarthritis (OA). Since oleanolic acid (OLA) have several pharmacological effects such as anti-inflammatory, anti-oxidant, we hypothesized it possesses protection against high glucose injured cartilage. We now report that OLA decreased type X collagen and reversed the cartilage degeneration in growth plate from db/db mice. OLA increased type Ⅱ collagen expression in a concentration-dependent manner (10-50 μΜ) in high glucose-treated chondrocytes. OLA prevented the high glucose induced cell injury and decreased the level of MMP-13, PGE2 and IL-6 due to decreasing mitochondrial membrane potential and stimulated the ATP production...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28645610/inhibition-of-mitochondrial-translation-effectively-sensitizes-renal-cell-carcinoma-to-chemotherapy
#2
Bo Wang, Aojin Song, Dan Yu, Ting Rao, Yuan Ruan, Xiaobin Yao
The functional importance of mitochondrial protein translation has been recently documented in the context of various cancers but not renal cell carcinoma (RCC). In lines with these efforts, our work demonstrates that mitochondrial translation inhibition by tigecycline or depletion of EF-Tu mitochondrial translation factor effectively targets RCC and significantly sensitizes RCC response to chemotherapy. We show that antibiotic tigecycline inhibits multiple biological functions of RCC, including growth, colony formation and survival...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28642839/the-mitochondrial-complex-i-ty-of-cancer
#3
REVIEW
Félix A Urra, Felipe Muñoz, Alenka Lovy, César Cárdenas
Recent evidence highlights that the cancer cell energy requirements vary greatly from normal cells and that cancer cells exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation. NADH-ubiquinone oxidoreductase (Complex I) is the largest complex of the mitochondrial electron transport chain and contributes about 40% of the proton motive force required for mitochondrial ATP synthesis. In addition, Complex I plays an essential role in biosynthesis and redox control during proliferation, resistance to cell death, and metastasis of cancer cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28642708/myricitrin-protects-cardiomyocytes-from-hypoxia-reoxygenation-injury-involvement-of-heat-shock-protein-90
#4
Min Wang, Gui-Bo Sun, Yu-Yang Du, Yu Tian, Ping Liao, Xue-Song Liu, Jing-Xue Ye, Xiao-Bo Sun
Modulation of oxidative stress is therapeutically effective in ischemia/reperfusion (I/R) injury. Myricitrin, a naturally occurring phenolic compound, is a potent antioxidant. However, little is known about its effect on I/R injury to cardiac myocytes. The present study was performed to investigate the potential protective effect of myricitrin against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. Myricitrin pretreatment improved cardiomyocyte viability, inhibited ROS generation, maintained the mitochondrial membrane potential, reduced apoptotic cardiomyocytes, decreased the caspase-3 activity, upregulated antiapoptotic proteins and downregulated proapoptotic proteins during H/R injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642134/mitochondrial-potassium-channels-in-cell-death
#5
Vanessa Checchetto, Michele Azzolini, Roberta Peruzzo, Paola Capitanio, Luigi Leanza
Mitochondria are intracellular organelles involved in several processes from bioenergetics to cell death. In the latest years, ion channels are arising as new possible targets in controlling several cellular functions. The discovery that several plasma membrane located ion channels have intracellular counterparts, has now implemented this consideration and the number of studies enforcing the understanding of their role in different metabolic pathways. In this review, we will discuss the recent updates in the field, focusing our attention on the involvement of potassium channels during mitochondrial mediated apoptotic cell death...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28642043/mitochondrial-cx43-an-important-component-of-cardiac-preconditioning
#6
REVIEW
Antonio Rodríguez-Sinovas, Marisol Ruiz-Meana, Amanda Denuc, David García-Dorado
Connexin 43 (Cx43) forms gap junction channels that are essential for the propagation of electrical depolarization in cardiomyocytes, but also with important roles in the pathophysiology of reperfusion injury. However, more recent studies have shown that Cx43 has also important functions independent from intercellular communication between adjacent cardiomyocytes. Some of these actions have been related to the presence of Cx43 in the mitochondria of these cells (mitoCx43). The functions of mitoCx43 have not been completely elucidated, but there is strong evidence indicating that mitoCx43 modulates mitochondrial respiration at respiratory complex I, production of radical oxygen species and ATP synthesis...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28633455/fetal-metabolic-stress-disrupts-immune-homeostasis-and-induces-pro-inflammatory-responses-in-hiv-1-and-cart-exposed-infants
#7
Johannes C Schoeman, Gontse P Moutloatse, Amy C Harms, Rob J Vreeken, Henriette J Scherpbier, Liesbeth Van Leeuwen, Taco W Kuijpers, Carools J Reinecke, Ruud Berger, Thomas Hankemeier, Madeleine J Bunders
Increased morbidity and fetal growth restriction are reported in uninfected children born to HIV-1-infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress skewing the cell's immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART)-exposure on the infants' immune-metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1-exposed infants, indicating altered mitochondrial functioning...
June 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28630339/ucp1-deficiency-causes-brown-fat-respiratory-chain-depletion-and-sensitizes-mitochondria-to-calcium-overload-induced-dysfunction
#8
Lawrence Kazak, Edward T Chouchani, Irina G Stavrovskaya, Gina Z Lu, Mark P Jedrychowski, Daniel F Egan, Manju Kumari, Xingxing Kong, Brian K Erickson, John Szpyt, Evan D Rosen, Michael P Murphy, Bruce S Kristal, Steven P Gygi, Bruce M Spiegelman
Brown adipose tissue (BAT) mitochondria exhibit high oxidative capacity and abundant expression of both electron transport chain components and uncoupling protein 1 (UCP1). UCP1 dissipates the mitochondrial proton motive force (Δp) generated by the respiratory chain and increases thermogenesis. Here we find that in mice genetically lacking UCP1, cold-induced activation of metabolism triggers innate immune signaling and markers of cell death in BAT. Moreover, global proteomic analysis reveals that this cascade induced by UCP1 deletion is associated with a dramatic reduction in electron transport chain abundance...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28615325/calcium-calmodulin-dependent-protein-kinase-regulates-the-pink1-parkin-and-dj-1-pathways-of-mitophagy-during-sepsis
#9
Xianghong Zhang, Du Yuan, Qian Sun, Li Xu, Emma Lee, Anthony J Lewis, Brian S Zuckerbraun, Matthew R Rosengart
During sepsis and shock states, mitochondrial dysfunction occurs. Consequently, adaptive mechanisms, such as fission, fusion, and mitophagy, are induced to eliminate damaged portions or entire dysfunctional mitochondria. The regulatory PINK1/Parkin and DJ-1 pathways are strongly induced by mitochondrial depolarization, although a direct link between loss of mitochondrial membrane potential (ΔΨ) and mitophagy has not been identified. Mitochondria also buffer Ca(2+), and their buffering capacity is dependent on ΔΨ...
June 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28612710/yc-1-induces-g0-g1-phase-arrest-and-mitochondria-dependent-apoptosis-in-cisplatin-resistant-human-oral-cancer-car-cells
#10
Miau-Rong Lee, Chingju Lin, Chi-Cheng Lu, Sheng-Chu Kuo, Je-Wei Tsao, Yu-Ning Juan, Hong-Yi Chiu, Fang-Yu Lee, Jai-Sing Yang, Fuu-Jen Tsai
Oral cancer is a serious and fatal disease. Cisplatin is the first line of chemotherapeutic agent for oral cancer therapy. However, the development of drug resistance and severe side effects cause tremendous problems clinically. In this study, we investigated the pharmacologic mechanisms of YC-1 on cisplatin-resistant human oral cancer cell line, CAR. Our results indicated that YC-1 induced a concentration-dependent and time-dependent decrease in viability of CAR cells analyzed by MTT assay. Real-time image analysis of CAR cells by IncuCyte™ Kinetic Live Cell Imaging System demonstrated that YC-1 inhibited cell proliferation and reduced cell confluence in a time-dependent manner...
June 2017: BioMedicine
https://www.readbyqxmd.com/read/28612103/dihydromyricetin-protects-human-umbilical-vein-endothelial-cells-from-injury-through-erk-and-akt-mediated-nrf2-ho-1-signaling-pathway
#11
Yun Luo, Shan Lu, Xi Dong, Lijia Xu, Guibo Sun, Xiaobo Sun
Atherosclerosis-related cardiovascular disease is the predominant cause of death worldwide. Ox-LDL-induced vascular endothelial cell injury is a major factor in the pathogenesis of atherosclerosis. Dihydromyricetin (DMY) is a flavonoid extracted from vine tea that exerts multiple pharmacological activities, including cardio-protective, anti-tumor, and anti-oxidative effects. However, it is unreported that DMY shows protective effects on ox-LDL-induced endothelial cell injury. In this study, we used an ox-LDL injured human umbilical vein endothelial cell (HUVEC) in vitro model to explore the protective effects and mechanism of DMY...
June 13, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28608291/iron-induced-generation-of-mitochondrial-ros-depends-on-ampk-activity
#12
Hui Huang, Jun Chen, Huiru Lu, Mengxue Zhou, Zhifang Chai, Yi Hu
Deregulated iron homeostasis is generally believed to be implicated in neurodegenerative diseases, including Parkinson's disease. Nevertheless, it is not fully understood how iron overload can elicit neuronal cell damage. Here we examined mitochondrial reactive oxygen species (ROS) levels in human dopaminergic neuroblastoma SH-SY5Y cells upon iron exposure. A relatively high concentration of iron could significantly increase mitochondrial ROS levels in SH-SY5Y cells. Pharmacological activation of AMP-activated protein kinase (AMPK) almost completely inhibited the effect of iron on mitochondrial ROS...
June 12, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28608258/extracts-of-chrysanthemum-zawadskii-attenuate-oxidative-damage-to-vascular-endothelial-cells-caused-by-a-highly-reducing-sugar
#13
Hyun-Sook Kim
Endothelial cells are considered candidates for involvement in the pathogenesis of diabetic vascular complications, and prevention of endothelial cell damage may be important in pharmacological attempts to prevent such complications. In the present study, I explored whether extracts of Chrysanthemum zawadskii (CZE) could prevent oxidative damage and dysfunction of a vascular endothelial cell line caused by the highly reducing sugar, 2-deoxy-D-ribose (dRib), and dysfunction of a vascular endothelial cell line...
June 12, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28606997/hpv-e7-induces-chemotherapy-mediated-tumor-suppression-by-ceramide-dependent-mitophagy
#14
Raquela J Thomas, Natalia Oleinik, Shanmugam Panneer Selvam, Silvia G Vaena, Mohammed Dany, Rose N Nganga, Ryan Depalma, Kyla D Baron, Jisun Kim, Zdzislaw M Szulc, Besim Ogretmen
Human papillomavirus (HPV) infection is linked to improved survival in response to chemo-radiotherapy for patients with oropharynx head and neck squamous cell carcinoma (HNSCC). However, mechanisms involved in increased HNSCC cell death by HPV signaling in response to therapy are largely unknown. Here, using molecular, pharmacologic and genetic tools, we show that HPV early protein 7 (E7) enhances ceramide-mediated lethal mitophagy in response to chemotherapy-induced cellular stress in HPV-positive HNSCC cells by selectively targeting retinoblastoma protein (RB)...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28603497/sigma-1-receptor-plays-a-negative-modulation-on-n-type-calcium-channel
#15
Kang Zhang, Zhe Zhao, Liting Lan, Xiaoli Wei, Liyun Wang, Xiaoyan Liu, Haitao Yan, Jianquan Zheng
The sigma-1 receptor is a 223 amino acids molecular chaperone with a single transmembrane domain. It is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes. By chaperone-mediated interactions with ion channels, G-protein coupled receptors and cell-signaling molecules, the sigma-1 receptor performs broad physiological and pharmacological functions. Despite sigma-1 receptors have been confirmed to regulate various types of ion channels, the relationship between the sigma-1 receptor and N-type Ca(2+) channel is still unclear...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28602868/protective-effects-of-oviductus-ranae-on-oxidative-stress-induced-apoptosis-in-rat-ovarian-granulosa-cells
#16
Xiao-Mei Ling, Xu-Hui Zhang, Yan Tan, Jing-Jing Yang, Bo Ji, Xin-Rong Wu, Yankui Yi, Lei Liang
ETHNOPHARMACOLOGICAL RELEVANCE: Oviductus Ranae (OR) is a traditional Chinese medicine derived from Rana temporaria chensinensis, and is known to have a wide variety of pharmacological effects. AIM OF THE STUDY: The aim of this study was to investigate the function and mechanism of OR in protecting rat ovarian granulosa cells from hydrogen peroxide (H2O2)-induced oxidative damage. MATERIALS AND METHODS: H2O2-treated granulosa cells were pretreated with OR-containing serum, and their viability and proliferation were evaluated using Cell Counting Kit-8 (CCK-8)...
June 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28600981/pharmacologic-concentrations-of-linezolid-modify-oxidative-phosphorylation-function-and-adipocyte-secretome
#17
Laura Llobet, M Pilar Bayona-Bafaluy, David Pacheu-Grau, Elena Torres-Pérez, José M Arbones-Mainar, M Ángeles Navarro, Covadonga Gómez-Díaz, Julio Montoya, Ester López-Gallardo, Eduardo Ruiz-Pesini
The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds...
May 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28600454/the-slo-w-path-to-identifying-the-mitochondrial-channels-responsible-for-ischemic-protection
#18
REVIEW
Charles Owen Smith, Keith Nehrke, Paul S Brookes
Mitochondria play an important role in tissue ischemia and reperfusion (IR) injury, with energetic failure and the opening of the mitochondrial permeability transition pore being the major causes of IR-induced cell death. Thus, mitochondria are an appropriate focus for strategies to protect against IR injury. Two widely studied paradigms of IR protection, particularly in the field of cardiac IR, are ischemic preconditioning (IPC) and volatile anesthetic preconditioning (APC). While the molecular mechanisms recruited by these protective paradigms are not fully elucidated, a commonality is the involvement of mitochondrial K(+) channel opening...
June 9, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28598851/mitochondrial-dysfunction-triggers-synaptic-deficits-via-activation-of-p38-map-kinase-signaling-in-differentiated-alzheimer-s-disease-trans-mitochondrial-cybrid-cells
#19
Qing Yu, Fang Du, Justin T Douglas, Haiyang Yu, Shirley ShiDu Yan, Shi Fang Yan
Loss of synapse and synaptic dysfunction contribute importantly to cognitive impairment in Alzheimer's disease (AD). Mitochondrial dysfunction and oxidative stress are early pathological features in AD-affected brain. However, the effect of AD mitochondria on synaptogenesis remains to be determined. Using human trans-mitochondrial "cybrid" (cytoplasmic hybrid) neuronal cells whose mitochondria were transferred from platelets of patients with sporadic AD or age-matched non-AD subjects with relatively normal cognition, we provide the first evidence of mitochondrial dysfunction compromises synaptic development and formation of synapse in AD cybrid cells in response to chemical-induced neuronal differentiation...
June 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28596418/err%C3%AE-maintains-mitochondrial-oxidative-metabolism-and-constitutes-an-actionable-target-in-pgc1%C3%AE-elevated-melanomas
#20
Pere Puigserver, Chi Luo, Eduardo Balsa, Ajith Thomas, Maximilian Hatting, Mark Jedrychowski, Steven P Gygi, Hans R Widlund
The uncontrolled growth of tumors provides metabolic dependencies that can be harnessed for therapeutic benefit. Although tumor cells exhibit these increased metabolic demands due to their rapid proliferation, these metabolic processes are general to all cells, and furthermore, targeted therapeutic intervention can provoke compensatory adaptation that alters tumors' characteristics. As an example, a subset of melanomas depends on the transcriptional coactivator PGC1α function to sustain their mitochondrial energy-dependent survival...
June 8, 2017: Molecular Cancer Research: MCR
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