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https://www.readbyqxmd.com/read/29329420/pyrrolidine-dithiocarbamate-reverses-bcl-xl-mediated-apoptotic-resistance-to-doxorubicin-by-inducing-paraptosis
#1
Seok Soon Park, Dong Min Lee, Jun Hee Lim, Dongjoo Lee, Sang Jun Park, Hwan Myung Kim, Seonghyang Sohn, Gyesoon Yoon, Young Woo Eom, Seong-Yun Jeong, Eun Kyung Choi, Kyeong Sook Choi
Elevated Bcl-xL expression in cancer cells contributes to DOX resistance, leading to failure in chemotherapy. In addition, the clinical use of high-dose doxorubicin (DOX) in cancer therapy has been limited by issues with cardiotoxicity and hepatotoxicity. Here, we show that co-treatment with pyrrolidine dithiocarbamate (PDTC) attenuates DOX-induced apoptosis in Chang-L liver cells and human hepatocytes, but overcomes DOX resistance in Bcl-xL-overexpressing Chang-L cells and several hepatocellular carcinoma (HCC) cell lines with high Bcl-xL expression...
January 10, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29328482/cytisine-induces-endoplasmic-reticulum-stress-caused-by-calcium-overload-in-hepg2-cells
#2
Lei Yu, Bo Jiang, Zhifeng Chen, Xin Wang, Dongxue Shang, Xiaopo Zhang, Yongxue Sun, Jinghui Yang, Yubin Ji
Cytisine, a quinolizidine alkaloid, is one of the major bioactive components found in the small tree Sophora Alopecuraides L., and is a traditional Chinese medicine that is used for treating hepatitis and liver cancer. In the 1960s, quinolizidine alkaloids were reported to exhibit inhibitory effects on tumour cell proliferation in several types of cancer cells. However, few studies have investigated the effect of cytisine on liver cancer. Our team confirmed that cytisine induced apoptosis in HepG2 cells via a mitochondrial pathway...
January 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29323715/alleviation-of-palmitic-acid-induced-endoplasmic-reticulum-stress-by-augmenter-of-liver-regeneration-through-ip3r-controlled-ca2-release
#3
Wei-Chun Xiao, Zhang Jing, Si-Li Chen, Yi-Jun Shi, Fan Xiao, Wei An
The aberrant release of Ca2+ from the endoplasmic reticulum (ER) contributes to the onset of ER stress, which is closely related to the pathogenesis of non-alcoholic fatty liver disease. We previously reported that augmenter of liver regeneration (ALR) alleviates ER stress and protects hepatocytes from lipotoxicity. However, the link between ALR protection and the suppression of ER stress remains unclear. In this study, we investigated whether the protection against liver steatosis afforded by ALR is related to its inhibition of calcium overflow from the ER to the mitochondria...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29316632/excessive-endoplasmic-reticulum-stress-correlates-with-impaired-mitochondrial-dynamics-mitophagy-and-apoptosis-in-liver-and-adipose-tissue-but-not-in-muscles-in-ems-horses
#4
Krzysztof Marycz, Katarzyna Kornicka, Jolanta Szlapka-Kosarzewska, Christine Weiss
Nowadays, endocrine disorders have become more frequent in both human and veterinary medicine. In horses, reduced physical activity combined with carbohydrate and sugar overload may result in the development of the so-called equine metabolic syndrome (EMS). EMS is characterized by insulin resistance, hyperinsulinemia, elevated blood triglyceride concentrations and usually obesity. Although the phenotypic features of EMS individuals are well known, the molecular mechanism underlying disease development remains elusive...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29312593/shikonin-induces-ros-based-mitochondria-mediated-apoptosis-in-colon-cancer
#5
Wenquan Liang, Jianxin Cui, Kecheng Zhang, Hongqing Xi, Aizhen Cai, Jiyang Li, Yunhe Gao, Chong Hu, Yi Liu, Yixun Lu, Ning Wang, Xiaosong Wu, Bo Wei, Lin Chen
Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29302508/alpers-huttenlocher-syndrome-first-presented-with-hepatic-failure-can-liver-transplantation-be-considered-as-treatment-option
#6
Sowon Park, Hoon-Chul Kang, Jin-Sung Lee, Young Nyun Park, Seung Kim, Hong Koh
Mitochondria play essential role in eukaryotic cells including in the oxidative phosphorylation and generation of adenosine triphosphate via the electron-transport chain. Therefore, defects in mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction which leads to various mitochondrial disorders that may present with various neurologic and non-neurologic manifestations. Mutations in the nuclear gene polymerase gamma (POLG) are associated with mtDNA depletions, and Alpers-Huttenlocher syndrome is one of the most severe manifestations of POLG mutation characterized by the clinical triad of intractable seizures, psychomotor regression, and liver failure...
December 2017: Pediatric Gastroenterology, Hepatology & Nutrition
https://www.readbyqxmd.com/read/29290907/morphological-alterations-and-redox-changes-associated-with-hepatic-warm-ischemia-reperfusion-injury
#7
Rim Jawad, Melroy D'souza, Lisa Arodin Selenius, Marita Wallenberg Lundgren, Olof Danielsson, Greg Nowak, Mikael Björnstedt, Bengt Isaksson
AIM: To study the effects of warm ischemia-reperfusion (I/R) injury on hepatic morphology at the ultrastructural level and to analyze the expression of the thioredoxin (TRX) and glutaredoxin (GRX) systems. METHODS: Eleven patients undergoing liver resection were subjected to portal triad clamping (PTC). Liver biopsies were collected at three time points; first prior to PTC (baseline), 20 min after PTC (post-ischemia) and 20 min after reperfusion (post-reperfusion)...
December 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/29290491/induction-of-apoptosis-by-pyrazolo-3-4-d-pyridazine-derivative-in-lung-cancer-cells-via-disruption-of-bcl-2-bax-expression-balance
#8
Mervat S Mohamed, Abdou O Abdelhamid, Fahad M Almutairi, Ayat G Ali, Mai K Bishr
In the rapidly expanding era of cancer target therapy, regulators of apoptosis are emerging as attractive therapeutic targets. X-linked inhibitor of apoptosis (XIAP) is of specific interest owing to its characteristic overexpression in a wide variety of neoplasms, with a resultant survival advantage for tumor cells and treatment resistance. In this study, we examined three pyrazolo [3,4-d] pyridazine derivatives (PPDs) through molecular modeling and studied their modes of interaction with XIAP-BIR3 domain. PPD-1, which possessed the highest binding affinity with XIAP, was tested on A549 (lung cancer cell line); HCT-116 (colorectal carcinoma cell line); HEPG2 (liver carcinoma cell line), HFB4 (normal human skin melanocyte cell line) and WI-38 (human embryonic lung fibroblasts)...
December 20, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29290359/nutritional-support-contributes-to-recuperation-in-a-rat-model-of-aplastic-anemia-by-enhancing-mitochondrial-function
#9
Guang Yang, Lifen Zhao, Bing Liu, Yujia Shan, Yang Li, Huimin Zhou, Li Jia
OBJECTIVES: Acquired aplastic anemia (AA) is a hematopoietic stem cell disease that leads to hematopoietic disorder and peripheral blood pancytopenia. We investigated whether nutritional support is helpful to AA recovery. METHODS: We established a rat model with AA. A nutrient mixture was administered to rats with AA through different dose gavage once per day for 55 d. Animals in this study were assigned to one of five groups: normal control (NC; group includes normal rats); AA (rats with AA); high dose (AA + nutritional mixture, 2266...
February 2018: Nutrition
https://www.readbyqxmd.com/read/29289830/the-synergistic-effects-of-waterborne-microcystin-lr-and-nitrite-on-hepatic-pathological-damage-lipid-peroxidation-and-antioxidant-responses-of-male-zebrafish
#10
Wang Lin, Jie Hou, Honghui Guo, Li Li, Lingkai Wang, Dandan Zhang, Dapeng Li, Rong Tang
Hazardous materials from decaying cyanobacterial blooms, such as microcystin-LR (MC-LR) and nitrite pose serious challenges to aquatic organisms. To assess combined toxic effects of MC-LR and nitrite on hepatic pathology, lipid peroxidation and antioxidant responses of fish, adult male zebrafish (Danio rerio) were exposed to solutions with different combined concentrations of MC-LR (0, 3, 30 μg/L) and nitrite (0, 2, 20 mg/L) for 30 d. The results showed that hepatic pathological lesions progressed in severity and extent with increasing concentration of single factor MC-LR or nitrite and became more severe in co-exposure groups...
December 28, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29289514/nutrient-excess-and-autophagic-deficiency-explaining-metabolic-diseases-in-obesity
#11
REVIEW
Gustav van Niekerk, André duToit, Ben Loos, Anna-Mart Engelbrecht
Over-nutrition and a sedentary lifestyle are the driving forces behind the development of metabolic diseases. Conversely, caloric restriction and exercise have proven to be the most effective strategies in combating metabolic diseases. Interestingly, exercise and caloric restriction share a common feature: both represent a potent mechanism for upregulating autophagy. Autophagy is rapidly induced by nutrient deprivation, and conversely, inactivated by amino acids as well as growth factors (e.g. insulin). Here, we review evidence demonstrating that autophagy may indeed be attenuated in metabolic tissue such as liver, muscle, and adipose, in the context of obesity...
December 28, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29288054/mitochondria-in-non-alcoholic-fatty-liver-disease
#12
Inês C M Simões, Adriana Fontes, Paolo Pinton, Hans Zischka, Mariusz R Wieckowski
NAFLD is a common disease in Western society and ranges from steatosis to steatohepatitis and to end-stage liver disease. The molecular mechanisms that cause the progression of steatosis to severe liver damage are not fully understood. One suggested mechanism involves the oxidation of biomolecules by mitochondrial ROS which initiates a vicious cycle of exacerbated mitochondrial dysfunction and increased hepatocellular oxidative damage. This may ultimately pave the way for hepatic inflammation and liver failure...
December 26, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29285057/chenodeoxycholic-acid-attenuates-high-fat-diet-induced-obesity-and-hyperglycemia-via-the-g-protein-coupled-bile-acid-receptor-1-and-proliferator-activated-receptor-%C3%AE-pathway
#13
Xiaosong Chen, Liu Yan, Zhihui Guo, Ying Chen, Ming Li, Chushan Huang, Zhaohong Chen, Xiyong Meng
G protein-coupled bile acid receptor 1 (TGR5) serves a key function in regulating glycometabolism. TGR5 is highly expressed in the mitochondria of brown adipose tissue (BAT) and downregulates adenosine triphosphate synthesis via the bile acid-TGR5-cyclic adenosine monophosphate-2-iodothyronine deiodinase (D2)-triiodothyronine-uncoupling protein pathway, thus regulating energy homeostasis and reducing body weight. Chenodeoxycholic acid (CDCA), the primary bile acid, is a natural ligand of TGR5. The present study aimed to characterize the ability of CDCA to reduce high-fat diet-induced obesity and improve glucose tolerance...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29282788/mpv17-related-mitochondrial-dna-maintenance-defect-new-cases-and-review-of-clinical-biochemical-and-molecular-aspects
#14
Ayman W El-Hattab, Julia Wang, Hongzheng Dai, Mohammed Almannai, Christian Staufner, Majid Alfadhel, Michael J Gambello, Pankaj Prasun, Saleem Raza, Hernando J Lyons, Manal Afqi, Mohammed A M Saleh, Eissa A Faqeih, Hamad I Alzaidan, Abduljabbar Alshenqiti, Leigh Anne Flore, Jozef Hertecant, Stephanie Sacharow, Deborah S Barbouth, Kei Murayama, Amit A Shah, Henry Lin, Lee-Jun C Wong
Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17 which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile-onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17-related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants...
December 27, 2017: Human Mutation
https://www.readbyqxmd.com/read/29277608/triptolide-induced-hepatotoxicity-can-be-alleviated-when-combined-with-panax-notoginseng-saponins-and-catapol
#15
Lingling Zhou, Cong Zhou, Zhe Feng, Zhangpu Liu, Huaxu Zhu, Xueping Zhou
ETHNOPHARMACOLOGICAL RELEVANCE: The hepatotoxicity of Tripterygium wilfordii Hook. f. (TW), due to the presence of triptolide (TP), limits its therapeutic potential. Based on the traditional Chinese medicine theory, the theory of "Yi lei xiang zhi" was proposed that Chinese herbs with different efficacy can restrict each other to achieve the least adverse reactions. AIM OF THE STUDY: To observe the effects of Catapol (CAT) and Panax notoginseng saponins (PNS), active ingredients in Rehmannia glutinosa (RG) and Panax notoginseng (PN) respectively, on reducing TP-induced hepatotoxicity, and further to explore the mechanisms...
December 22, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29277577/coronaridine-congeners-modulate-mitochondrial-%C3%AE-3%C3%AE-4-nicotinic-acetylcholine-receptors-with-different-potency-and-through-distinct-intra-mitochondrial-pathways
#16
Hugo R Arias, Olena Lykhmus, Kateryna Uspenska, Maryna Skok
In contrast to plasma membrane-expressed nicotinic acetylcholine receptors (nAChRs), mitochondrial nAChRs function in an ion-independent manner by triggering intra-mitochondrial kinases that regulate the release of cytochrome c (Cyt c), an important step in cellular apoptosis. The aim of this study is to determine the structural requirements for mitochondrial α3β4* nAChR activation by measuring the modulatory effects of two noncompetitive antagonists of these receptors, (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC], on Cyt c release from wild-type and α7-/- mice mitochondria...
December 22, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29274570/characterization-of-the-impact-of-glutaredoxin-2-grx2-deficiency-on-superoxide-hydrogen-peroxide-release-from-cardiac-and-liver-mitochondria
#17
Julia Chalker, Danielle Gardiner, Nidhi Kuksal, Ryan J Mailloux
Mitochondria are critical sources of hydrogen peroxide (H2O2), an important secondary messenger in mammalian cells. Recent work has shown that O2•-/H2O2 emission from individual sites of production in mitochondria is regulated by protein S-glutathionylation. Here, we conducted the first examination of O2•-/H2O2 release rates from cardiac and liver mitochondria isolated from mice deficient for glutaredoxin-2 (GRX2), a matrix-associated thiol oxidoreductase that facilitates the S-glutathionylation and deglutathionylation of proteins...
December 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/29246127/high-mobility-group-box-1-promotes-sorafenib-resistance-in-hepg2-cells-and-in-vivo
#18
Yinzong Xiao, Lunquan Sun, Yongming Fu, Yan Huang, Rongrong Zhou, Xingwang Hu, Pengcheng Zhou, Jun Quan, Ning Li, Xue-Gong Fan
BACKGROUND: Primary liver cancer is a lethal malignancy with a high mortality worldwide. Currently, sorafenib is the most effective molecular-targeted drug against hepatocellular carcinoma (HCC). However, the sorafenib resistance rate is high. The molecular mechanism of this resistance has not been fully elucidated. High mobility group box 1 (HMGB1) is a multifaceted protein that plays a key role in the proliferation, apoptosis, metastasis and angiogenesis of HCC cells. In addition, HMGB1 has been suggested to contribute to chemotherapy resistance in tumours, including lung cancer, osteosarcoma, neuroblastoma, leukaemia, and colorectal cancer...
December 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29243082/dihydroquercetin-ameliorated-acetaminophen-induced-hepatic-cytotoxicity-via-activating-jak2-stat3-pathway-and-autophagy
#19
Wenjing Zai, Wei Chen, Jingyun Luan, Jiajun Fan, Xuyao Zhang, Zimei Wu, Tao Ding, Dianwen Ju, Hongrui Liu
Acetaminophen (APAP) overdose is currently the leading cause of acute liver disease, but therapeutic treatment strategies are commonly limited. Although dihydroquercetin (DHQ) is an attractive botanical antioxidant, its protective potential for liver disease remains elusive. The present study investigated the protective effects of DHQ against APAP-induced hepatic cytotoxicity. Primary mouse hepatocytes were treated with different concentrations of DHQ followed by APAP administration. Our data showed that DHQ relieved APAP-induced growth inhibition and lactate dehydrogenase (LDH) release in a dose-dependent manner, as well as inhibited APAP-induced necrosis and extracellular signal regulated kinase-c-Jun-N-terminal kinase (ERK-JNK) stress...
December 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29243009/adrenaline-induces-mitochondrial-biogenesis-in-rat-liver
#20
Gaetana Napolitano, Daniela Barone, Sergio Di Meo, Paola Venditti
We studied the effects of adrenaline administration and depletion (induced by reserpine) on rat liver oxidative metabolism. We showed that adrenaline increases, and reserpine decreases aerobic capacity (inferred by cytochrome oxidase activity) in tissue modifying the hepatic content of mitochondrial proteins without changing mitochondrial aerobic capacity. The changes in tissue cytochrome oxidase activity, which agreed with the expression levels of factors involved in mitochondrial biogenesis, such as PGC-1, NRF-1, and NRF-2, were associated with similar changes in tissue and mitochondrial State 3 respiration...
December 14, 2017: Journal of Bioenergetics and Biomembranes
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