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Mitochondrial apoptosis

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https://www.readbyqxmd.com/read/28225005/autophagy-protects-against-palmitic-acid-induced-apoptosis-in-podocytes-in-vitro
#1
Xu-Shun Jiang, Xue-Mei Chen, Jiang-Min Wan, Hai-Bo Gui, Xiong-Zhong Ruan, Xiao-Gang Du
Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224980/alpha-synuclein-prevents-the-formation-of-spherical-mitochondria-and-apoptosis-under-oxidative-stress
#2
Stefanie Menges, Georgia Minakaki, Patrick M Schaefer, Holger Meixner, Iryna Prots, Ursula Schlötzer-Schrehardt, Kristina Friedland, Beate Winner, Tiago F Outeiro, Konstanze F Winklhofer, Christine A F von Arnim, Wei Xiang, Jürgen Winkler, Jochen Klucken
Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson's disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in neural cells. We characterize a distinct type of mitochondrial fragmentation, following H2O2 or 6-OHDA-induced OS, defined by spherically-shaped and hyperpolarized mitochondria, termed "mitospheres"...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224421/essential-oil-from-siegesbeckia-pubescens-induces-apoptosis-through-the-mitochondrial-pathway-in-human-hepg2-cells
#3
Dan Lv, Kai-Wen Guo, Chan Xu, Mi Huang, Si-Jian Zheng, Xin-Hua Ma, Li-Hong Pan, Qiang Wang, Xin-Zhou Yang
Siegesbeckia pubescens (SP) has been used as a traditional medicine for the treatment of and inflammatory diseases. However, the activities of SP against hepatocellular carcinoma and the related mechanisms remain unclear. The present study aimed to examine the effects of the essential oil of SP (SPEO) on the proliferation of hepatocellular carcinoma cells and the possible mechanisms. The growth inhibition of HepG2 cells was analyzed by MTT assay. Hoechst 33258 and fluorescence microscopy were utilized to observe the nuclear morphological changes of apoptotic cells...
February 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28224196/calcium-and-oxidative-stress-mediate-perillaldehyde-induced-apoptosis-in-candida-albicans
#4
Hui Tian, Su Qu, Yanzhen Wang, Zhaoqun Lu, Man Zhang, Yeyun Gan, Peng Zhang, Jun Tian
New anti-Candida albicans drugs are needed due to the emergence of resistant cases in recent years. Perillaldehyde (PAE) is a natural monoterpenoid compound derived from Perilla frutescens. The minimum inhibitory concentration of PAE against C. albicans was 0.4 μL/mL. We aimed to elucidate the antifungal mode of action of PAE against C. albicans. The antifungal activity of PAE against C. albicans was found to correlate with an elevation in intracellular Ca(2+) and accumulation of ROS. Several downstream apoptosis events such as the disruption of mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation were observed in PAE-treated cells...
February 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28223427/calcium-dependent-enhancement-by-extracellular-acidity-of-the-cytotoxicity-of-mitochondrial-inhibitors-against-melanoma
#5
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Since acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223230/myotoxicity-of-statins-mechanism-of-action
#6
REVIEW
Patrick du Souich, Ghislaine Roederer, Robert Dufour
Statins are effective drugs to reduce cardiovascular events secondary to dyslipidemia; however, they cause frequent undesirable side effects. The incidence of statin-induced myotoxicity (SIM) is presented by 7 to 29% of patients, depending upon the report. SIM may develop in presence of abnormally high concentrations of statins in the myocyte and/or in presence of muscular conditions that may predispose to SIM. High concentrations of statins in the myocyte may occur whenever the activity of liver influx membrane transporters, namely OATP1B1, of drug metabolizing enzymes, and of liver and muscular efflux transporters, MDR1 and BCRP, is reduced...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28222421/luteolin-enhances-sarcoplasmic-reticulum-ca2-atpase-activity-through-p38-mapk-signaling-thus-improving-rat-cardiac-function-after-ischemia-reperfusion
#7
Shasha Zhu, Tongda Xu, Yuanyuan Luo, Yingying Zhang, Haochen Xuan, Yanfeng Ma, Defeng Pan, Dongye Li, Hong Zhu
BACKGROUND/AIMS: A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism. METHODS: Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R...
February 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28222054/ucp2-expression-is-increased-in-pancreas-from-brain-dead-donors-and-involved-in-cytokine-induced-%C3%AE-cells-apoptosis
#8
Leticia A Brondani, Tatiana H Rech, Gabriela Boelter, Andrea C Bauer, Cristiane B Leitão, Décio L Eizirik, Daisy Crispim
BACKGROUND: Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in β cell apoptosis, but these findings remain controversial...
March 2017: Transplantation
https://www.readbyqxmd.com/read/28221789/raman-spectroscopy-reveals-selective-interactions-of-cytochrome-c-with-cardiolipin-that-correlate-with-membrane-permeability
#9
Jay P Kitt, David A Bryce, Shelley D Minteer, Joel M Harris
Permeabilization of the outer mitochondrial membrane is an integral step in apoptosis. The resulting release of pro-apoptotic signaling proteins leads to cell destruction through activation of the cysteine-aspartic protease (caspase) cascade. However, the mechanism of outer mitochondrial membrane (OMM) permeabilization remains unclear. It was recently shown that cytochrome c can induce pore formation in cardiolipin-containing phospholipid membranes leading to large dextran and protein permeability. In this work, the interaction of cytochrome c with cardiolpin-containing phospholipid vesicles, serving as models of the OMM, is investigated to probe cytochrome c-induced permeability...
February 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28220885/cancer-cell-mitochondria-targeting-by-pancratistatin-analogs-is-dependent-on-functional-complex-ii-and-iii
#10
Dennis Ma, Christopher Pignanelli, Daniel Tarade, Tyler Gilbert, Megan Noel, Fadi Mansour, Scott Adams, Alexander Dowhayko, Kyle Stokes, Sergey Vshyvenko, Tomas Hudlicky, James McNulty, Siyaram Pandey
Enhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220655/ppars-in-the-central-nervous-system-roles-in-neurodegeneration-and-neuroinflammation
#11
Juan M Zolezzi, Manuel J Santos, Sussy Bastías-Candia, Claudio Pinto, Juan A Godoy, Nibaldo C Inestrosa
Over 25 years have passed since peroxisome proliferators-activated receptors (PPARs), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand-activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro...
February 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28220405/altered-cellular-homeostasis-in-murine-mps-i-fibroblasts-evidence-of-cell-specific-physiopathology
#12
Gustavo Monteiro Viana, Cinthia Castro do Nascimento, Edgar Julian Paredes-Gamero, Vânia D'Almeida
Mucopolysaccharidosis type I (MPS I), a rare autosomal recessive disease, is caused by a deficiency of the lysosomal enzyme alfa-L-iduronidase. Impaired enzyme activity promotes glycosaminoglycans accumulation in several tissues and organs, leading to complex multisystemic complications. Several studies using animal models indicated different intracellular pathways involving MPS I physiopathology; however, the exact mechanisms underlying this syndrome are still not understood. Previous results from our group showed alterations in ionic homeostasis and cell viability of splenocytes and macrophages in Idua-/- mice...
February 21, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28220271/anandamide-oxidative-metabolism-induced-endoplasmic-reticulum-stress-and-apoptosis
#13
M Almada, B M Fonseca, C Amaral, M Diniz-da-Costa, G Correia-da-Silva, N Teixeira
The Endocannabinoid System (ECS) has been recognized as a crucial player in human reproduction. Changes in the levels of anandamide (AEA), the main endocannabinoid (eCB), negatively affect reproductive events, such as implantation, decidualization and placentation. Cyclooxygenase-2 (COX-2) is a major enzyme expressed in the endometrium and its involvement in female reproductive system has evolved over the last few years. Currently, COX-2 oxidative metabolism is emerging as a key mediator of AEA-induced actions...
February 20, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28220193/hsa-mir-4485-regulates-mitochondrial-functions-and-inhibits-the-tumorigenicity-of-breast-cancer-cells
#14
Lakshmi Sripada, Kritarth Singh, Anastasiya V Lipatova, Aru Singh, Paresh Prajapati, Dhanendra Tomar, Khyati Bhatelia, Milton Roy, Rochika Singh, Madan M Godbole, Peter M Chumakov, Rajesh Singh
The modulation of mitochondrial functions is important for maintaining cellular homeostasis. Mitochondria essentially depend on the import of RNAs and proteins encoded by the nuclear genome. MicroRNAs encoded in the nucleus can translocate to mitochondria and target the genome, affecting mitochondrial function. Here, we analyzed the role of miR-4485 in the regulation of mitochondrial functions. We showed that miR-4485 translocated to mitochondria where its levels varied in response to different stress conditions...
February 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28220125/hgf-secreted-by-activated-kupffer-cells-induces-apoptosis-of-plasmodium-infected-hepatocytes
#15
Lígia Antunes Gonçalves, Joana Rodo, Lurdes Rodrigues-Duarte, Luciana Vieira de Moraes, Carlos Penha-Gonçalves
Malaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium-infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219713/effect-of-doxorubicin-induced-ovarian-toxicity-on-mouse-ovarian-granulosa-cells
#16
Ting Zhang, Wan Hong He, Ling Lin Feng, Hao Guang Huang
The objective of this study was to identify the effect of doxorubicin-induced ovarian toxicity on mouse ovarian granulosa cells. After granulosa cells were treated with doxorubicin at the final concentrations of 0, 0.4, 0.8, and 1.6 μg/ml for 24 h, cell apoptosis was detected by DAPI staining or caspase-3/7 fluorescence probe; ROS was determined by 2', 7'-dichlorodihydrofluorescin diacetate fluorescence probe; mitochondrial membrane potential was detected by rhodamine-123 fluorescence probe; and mRNA expression levels of Bax, Bcl-2, p53, FSHR, StAR, P450scc and P450arom were analyzed by RT-PCR...
February 17, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28219700/inhibition-of-ros-production-autophagy-or-apoptosis-signaling-reversed-the-anticancer-properties-of-antrodia-salmonea-in-triple-negative-breast-cancer-mda-mb-231-cells
#17
Chia-Ting Chang, Mallikarjuna Korivi, Hui-Chi Huang, Varadharajan Thiyagarajan, Kai-Yuan Lin, Pei-Jane Huang, Jer-Yuh Liu, You-Cheng Hseu, Hsin-Ling Yang
We investigated the in vitro and in vivo anticancer properties of Antrodia salmonea (AS), a well-known edible/medicinal mushroom in Taiwan, on human triple-negative breast cancer (MDA-MB-231) cells and xenografted nude mice; and revealed the underlying molecular mechanisms involved in autophagic- and apoptotic-cell death. Treatment of MDA-MB-231 cells with fermented culture broth of AS (0-200 μg/mL) inhibited cell viability/growth. AS-induced autophagy was evidenced via increased LC3-II accumulation, GFP-LC3 puncta and AVOs formation in MDA-MB-231 cells...
February 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28219650/dendritic-cells-death-induced-by-contact-sensitizers-is-controlled-by-nrf2-and-depends-on-glutathione-levels
#18
Zeina El Ali, Claudine Deloménie, Jérémie Botton, Marc Pallardy, Saadia Kerdine-Römer
Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action...
February 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28218651/proteome-characteristics-of-non-alcoholic-steatohepatitis-liver-tissue-and-associated-hepatocellular-carcinomas
#19
Anna Kakehashi, Vasily E Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, Hideki Wanibuchi
To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218611/auranofin-an-inhibitor-of-thioredoxin-reductase-induces-apoptosis-in-hepatocellular-carcinoma-hep3b-cells-by-generation-of-reactive-oxygen-species
#20
Hyun Hwang-Bo, Jin-Woo Jeong, Min Ho Han, Cheol Park, Su-Hyun Hong, Gi-Young Kim, Sung-Kwon Moon, Jaehun Cheong, Wun-Jae Kim, Young Hyun Yoo, Yung Hyun Choi
Mammalian thioredoxin reductase (TrxR) plays a vital role in restoring cellular redox balance disrupted by reactive oxygen species (ROS) generation and oxidative damage. Here, we evaluated whether auranofin, a selective inhibitor of TrxR, could serve as a potential anti-cancer agent through its selective targeting of TrxR activity in Hep3B hepatocellular carcinoma cells. Auranofin treatment reduced the TrxR activity of these cells and induced apoptosis, which were accompanied by up-regulation of death receptors (DRs) and activation of caspases, as well as promotion of proteolytic degradation of poly(ADP-ribose)-polymerase...
February 20, 2017: General Physiology and Biophysics
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