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Mitochondrial Membrane Potential

Ayako Kumagai, Tsutomu Sasaki, Kenta Matsuoka, Masayoshi Abe, Toshihide Tabata, Yumi Itoh, Hiroyuki Fuchino, Sartagul Wugangerile, Mika Suga, Tomoko Yamaguchi, Hidehisa Kawahara, Yasuo Nagaoka, Kenji Kawabata, Miho Kusuda Furue, Hiroshi Takemori
Dysfunction of mitochondrial activity is often associated with the onset and progress of neurodegenerative diseases. Membrane depolarization induced by Na+ influx increases intracellular Ca2+ levels in neurons, which upregulates mitochondrial activity. However, overlimit of Na+ influx and its prolonged retention ultimately cause excitotoxicity leading to neuronal cell death. To return the membrane potential to the normal level, Na+ /K+ -ATPase exchanges intracellular Na+ with extracellular K+ by consuming a large amount of ATP...
August 18, 2018: Synapse
Paulina Jędrak, Paweł Mozolewski, Grzegorz Węgrzyn, Mariusz R Więckowski
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder manifesting as progressive impairment of motor function and different neuropsychiatric symptoms caused by an expansion of CAG repeats in huntingtin gene (HTT). Mitochondrial dysfunction and bioenergetic defects can contribute to the course of the disease, however, the molecular mechanism underlying this process is still largely unknown. In this study, we aimed to determine several mitochondrial parameters in HD fibroblasts and assess their relevance to the disease progression as well as to value mitochondrial pathology in peripheral cells as disease potential biomarker...
August 17, 2018: Metabolic Brain Disease
Valeria Padovano, Christine Podrini, Alessandra Boletta, Michael J Caplan
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, potentially lethal, monogenic diseases and is caused predominantly by mutations in polycystic kidney disease 1 (PKD1) and PKD2, which encode polycystin 1 (PC1) and PC2, respectively. Over the decades-long course of the disease, patients develop large fluid-filled renal cysts that impair kidney function, leading to end-stage renal disease in ~50% of patients. Despite the identification of numerous dysregulated pathways in ADPKD, the molecular mechanisms underlying the renal dysfunction from mutations in PKD genes and the physiological functions of the polycystin proteins are still unclear...
August 17, 2018: Nature Reviews. Nephrology
Yung Hyun Choi
The generation of excessive reactive oxygen species (ROS) by oxidative stress has various deleterious effects on cellular constituents. Therefore, the discovery of natural products that can inhibit the production of ROS may be effective in suppressing the onset and treatment of oxidative stress-mediated diseases. Despite the antioxidant efficacy studies on various substances in the genus Schisandra used as traditional medicine, research on the efficacy of schisandrin A, a class of active lignans, remains insufficient...
July 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Juliana da Trindade Granato, Juliana Alves Dos Santos, Stephane Lima Calixto, Natália Prado da Silva, Jefferson da Silva Martins, Adilson David da Silva, Elaine Soares Coimbra
The search for new drugs for the treatment of leishmaniasis is an important strategy for improving the current therapeutic arsenal for the disease. There are several limitations to the available drugs including high toxicity, low efficacy, prolonged parenteral administration, and high costs. Steroids are a diverse group of compounds with various applications in pharmacology. However, the antileishmanial activity of this class of molecules has not yet been explored. Therefore, in the present study, we investigated the antileishmanial activity and cytotoxicity of novel steroids against murine macrophages with a focus on the derivatives of cholesterol (CD), cholic acid (CA), and deoxycholic acid (DA)...
July 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hyejin Kim, Sung Won Kim, Kwang Hyuk Seok, Chi Woo Hwang, Jin-Chul Ahn, Jun-O Jin, Hyun Wook Kang
BACKGROUND: Hypericin (HYP) extracted from St. John's wort ( Hypericum perforatum L.) is a natural photosensitizer in clinical photodynamic therapy (PDT). The PDT is one of the powerful methods for cancer treatments because of its excellent tumoritropic characteristics and photosensitizing properties. However, limited reports on the efficacy of PDT on the anaplastic thyroid cancer (ATC) have been published. Especially HYP-associated PDT has not been investigated in vitro and in vivo. In this study, we evaluated the effect of HYP for PDT against FRO ATC cells...
August 14, 2018: Photodiagnosis and Photodynamic Therapy
Thamara Figueiredo Procópio, Leydianne Leite de Siqueira Patriota, Bárbara Rafaela da Silva Barros, Lethícia Maria de Souza Aguiar, Virgínia Maria Barros de Lorena, Patrícia Maria Guedes Paiva, Cristiane Moutinho Lagos de Melo, Thiago Henrique Napoleão
CasuL is a lectin (carbohydrate-binding protein) isolated from the leaf pinnulae of Calliandra surinamensis that is toxic against cancer cells. In this study, the effects of CasuL on the activation of immune cells were evaluated in BALB/c mice splenocytes. Assays measuring the changes in cytosolic calcium concentration ([Ca2+ ]cyt ), mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) levels associated with cell viability, proliferation, and cytokine and nitric oxide production were performed...
August 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Javier Quero, Silvia Cabello, Teresa Fuertes, Inés Mármol, Ruben Laplaza, Victor Polo, M Concepción Gimeno, Ma Jesús Rodriguez-Yoldi, Elena Cerrada
New mixed gold(III) derivatives with dithiocarbamate and thiolate ligands have been synthesized and characterized. They display high anticancer activity against colon cancer cell lines without affecting to differentiated enterocytes, high stability in phosphate-buffered saline solution, and resistance to gold reduction in the presence of reducing agents in the majority of the derivatives. Some of them show interaction with thioredoxin reductase as derived from in vitro analysis and computational studies. However, a competition between this enzyme and proteasome is detected in cells, which is corroborated by the determination of proteasomal chymotrypsin-like activity inhibition...
August 17, 2018: Inorganic Chemistry
Tímea Komlódi, Fanni F Geibl, Matilde Sassani, Attila Ambrus, László Tretter
Succinate-driven reverse electron transport (RET) is one of the main sources of mitochondrial reactive oxygen species (mtROS) in ischemia-reperfusion injury. RET is dependent on mitochondrial membrane potential (Δψm ) and transmembrane pH difference (ΔpH), components of the proton motive force (pmf); a decrease in Δψm and/or ΔpH inhibits RET. In this study we aimed to determine which component of the pmf displays the more dominant effect on RET-provoked ROS generation in isolated guinea pig brain and heart mitochondria respiring on succinate or α-glycerophosphate (α-GP)...
August 17, 2018: Journal of Bioenergetics and Biomembranes
Xueling Zou, Wenfeng Huang
A steroidal saponin named pennogenin 3-O-α-L-rhamnopyranosyl-(1→2) [α-L-rhamnopyranosyl-(1→4)]-β-D-glucoyranoside(TTB2) has been successfully separated from the n-BuOH extracts of Trillium tschonoskii Maxim and is able to induce cytotoxicity to some types cancer cells. The present study aimed to investigate how this novel saponinin duces cytotoxicity in malignant sarcoma cells and to clarify its molecular mechanisms of action. It was determined this steroidal saponin induced the apoptosis in Rh1 cells and activated caspase-3 and caspase-9...
August 2018: Experimental and Therapeutic Medicine
Przemysław Sitarek, Ewelina Synowiec, Tomasz Kowalczyk, Tomasz Śliwiński, Ewa Skała
As the current cancer treatment success rate is not sufficient, interest has grown in plants as possible sources of anti-cancer compounds. One such plant with a broad spectrum of activity is Lenourus sibiricus of the family Lamiaceae. This study investigates for the first time both the genotoxic and cytotoxic activities of TR (transformed) and AtPAP1 TR (with over-expression of transcriptional factor) root extracts of Lenourus sibiricus against various cancer cell lines (CCRF-CEM, K-562 and A549). Both tested extracts showed a cytotoxic effect on CCRF-CEM and K-562 cell lines, but strongest activity was observed for the AtPAP1 TR extract...
August 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
J-G Cai, L-M Luo, H Tang, L Zhou
One of the end-products of ROS-induced peroxidation, malondialdehyde (MDA), induces the cross-links in proteins, which leads to perturbation of the physiological functions of cells and contributes to abnormal biological regulation and various disorders. Taurine (2-aminoethanesulfonic acid, Tau) aids in adjusting normal physiological functions to confer stress resistance. The protective effects of Tau against MDA stress in vitro or in vivo were reported previously. In this study, we had investigated the protective effects of taurine on viability, oxidative stress levels and mitochondrial biogenesis in mouse muscle C2C12 cells undergoing MDA induced stress...
July 2018: Molekuliarnaia Biologiia
Catia Santos Branco, Angela Duong, Alencar K Machado, Gustavo Scola, Ana C Andreazza, Mirian Salvador
Araucaria angustifolia extract (AAE) is a polyphenol-rich extract that has gained interest as a natural anticancer agent. Recent work suggests that AAE induces oxidative damage and apoptosis through its action on decreasing complex I activity of the mitochondrial electron transport chain (ETC). In the present study, we aimed to further examine the specific targets by which AAE exerts pro-apoptotic effects in HEp-2 cancer cells. Specifically, the effect of AAE on the: 1) levels of pyruvate dehydrogenase was assessed by ELISA assay; 2) levels of mitochondrial ETC complexes, focusing on complex I at the gene transcript and protein level relevant to ROS generation was evaluated by multiplex ELISA followed by qRT-PCR and immunoblotting; 3) mitochondrial membrane potential (ΔΨm) was assessed by MitoTracker Red CMXRos; and 4) chemical variations on DNA was evaluated by dot-blotting in HEp-2 cells...
August 16, 2018: Anti-cancer Agents in Medicinal Chemistry
Stefanie J Oeding, Katarzyna Majstrowicz, Xiao-Ping Hu, Vera Schwarz, Angelika Freitag, Ulrike Honnert, Petra Nikolaus, Martin Bähler
Mitochondrial distribution in cells is critical for cellular function and proper inheritance during cell division. In mammalian cells, mitochondria are transported predominantly along microtubules by kinesin and dynein motors that bind indirectly via TRAK1/2 to outer mitochondrial membrane proteins Miro1/2. Here, using proximity labeling, we identified Miro1/2 as potential binding partners of myosin XIX (Myo19). Interaction studies show that Miro1 binds directly to a C-terminal fragment of the Myo19 tail region and that Miro recruits the Myo19 tail in vivo This recruitment is regulated by the nucleotide-state of the N-terminal Rho-like GTPase domain of Miro...
August 15, 2018: Journal of Cell Science
Pierre-Andre Barbeau, Paula M Miotto, Graham P Holloway
The mechanisms regulating oxidative phosphorylation during exercise remain poorly defined, however key mitochondrial proteins, including carnitine-palmitoyl transferase-I (CPT-I) and adenine-nucleotide translocase have redox sensitive sites. Interestingly muscle contraction has recently been shown to increase mitochondrial membrane potential and reactive oxygen species (ROS) production, therefore we aimed to determine if mitochondrial derived ROS influences bioenergetic responses to exercise. Specifically, we examined the influence of acute exercise on mitochondrial bioenergetics in WT and transgenic mice (MCAT) possessing attenuated mitochondrial ROS...
August 15, 2018: Biochemical Journal
You-Jiang Yu, Ji-Lin Ye, Jian-Ming Peng, Ai-Lian Wu, Dong-Yan Wang, Yan-Qing Liu
OBJECTIVE: To explore the effects of Osthole on apoptosis of HL-60 cells induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL) and its possible mechanism. METHODS: The proliferative inhibition of HL-60 cells treated with different concentrations of Osthole, TRAIL alone and Osthole combined with TRAIL was measured by MTT assay. The HL-60 cells were treated with Osthole, TRAIL alone and Osthole combined with TRAIL at the concentration<IC50 value, i...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Anneleen Steels, Adriaan Verhelle, Olivier Zwaenepoel, Jan Gettemans
The tumor suppressor p53 is of crucial importance in the prevention of cellular transformation. In the presence of cellular stress signals, the negative feedback loop between p53 and Mdm2, its main negative regulator, is disrupted, which results in the activation and stabilization of p53. Via a complex interplay between both transcription-dependent and - independent functions of p53, the cell will go through transient cell cycle arrest, cellular senescence or apoptosis. However, it remains difficult to completely fathom the mechanisms behind p53 regulation and its responses, considering the presence of multiple layers involved in fine-tuning them...
August 15, 2018: MAbs
Kishore Mullagiri, V Lakshma Nayak, Satish Sunkari, Geeta Sai Mani, Sravanthi Devi Guggilapu, Burri Nagaraju, Abdullah Alarifi, Ahmed Kamal
A series of new (3-(1 H -benzo[ d ]imidazol-2-yl))/(3-(3 H -imidazo[4,5- b ]pyridin-2-yl))-(1 H -indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates 4-6(a-i) were synthesized and evaluated for their antiproliferative activity on selected human cancer cell lines such as prostate (DU-145), lung (A549), cervical (HeLa) and breast (MCF-7). Most of these conjugates showed considerable cytotoxicity with IC50 values ranging from 0.54 to 31.86 μM. Among them, compounds 5g and 6f showed significant activity against human prostate cancer cell line DU-145 with IC50 values of 0...
February 1, 2018: MedChemComm
Marcel König, Daniel Siegmund, Lukasz J Raszeja, Aram Prokop, Nils Metzler-Nolte
Emerging resistances of tumors against multiple anti-cancer agents are a major concern in the chemotherapeutical treatment of various cancers. Clearly, this raises the need for novel therapeutics with new modes of action. Herein, we report on the favorable in vitro anti-proliferative properties of a phenanthridine-containing ReI (CO)3 complex (compound 1 , also abbreviated LR-166) and identify major contributions to its mode of action. The complex induces apoptosis in low micromolar concentrations even in drug-resistant Burkitt-like lymphoma (BJAB) and leukemia (Nalm-6) cell lines with known overexpression of p -glycoproteins as was confirmed by measuring the amount of hypodiploid DNA via FACS Scan analysis...
January 1, 2018: MedChemComm
Tomohiro Omura, Miwa Sasaoka, Gaia Hashimoto, Satoshi Imai, Joe Yamamoto, Yuki Sato, Shunsaku Nakagawa, Atsushi Yonezawa, Takayuki Nakagawa, Ikuko Yano, Yoshikazu Tasaki, Kazuo Matsubara
We have previously reported that oxicam-derived non-steroidal anti-inflammatory drugs (oxicam-NSAIDs), including meloxicam, piroxicam and tenoxicam, elicit protective effects against 1-methyl-4-phenyl pyridinium (MPP+ )-induced cell death in a fashion independent of cyclooxygenase (COX) inhibition. We have also demonstrated that oxicam-NSAIDs suppress the decrease in phosphorylation of Akt caused by MPP+ . The molecular mechanism through which oxicam-NSAIDs provide cytoprotection remains unclear. In this study, we speculated a possibility that endoplasmic reticulum (ER) stress and/or mitochondrial dysfunction, which are both causative factors of Parkinson's disease (PD), may be involved in the neuroprotective mechanism of oxicam-NSAIDs...
August 11, 2018: Biochemical and Biophysical Research Communications
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