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https://www.readbyqxmd.com/read/29035972/hyperammonemia-and-proteostasis-in-cirrhosis
#1
Srinivasan Dasarathy, Maria Hatzoglou
PURPOSE OF REVIEW: Skeletal muscle loss or sarcopenia is a frequent complication of cirrhosis that adversely affects clinical outcomes. As skeletal muscle is the largest store of proteins in the body, proteostasis or protein homeostasis is required for maintenance of muscle mass. This review will focus on disordered skeletal muscle proteostasis in liver disease. RECENT FINDINGS: Increased skeletal muscle uptake of ammonia initiates responses that result in disordered proteostasis including impaired protein synthesis and increased autophagy...
October 14, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29035693/mms19-localizes-to-mitochondria-and-protects-the-mitochondrial-genome-from-oxidative-damage
#2
Rui Wu, Qunsong Tan, Kaifeng Niu, Yuqi Zhu, Di Wei, Yongliang Zhao, Hongbo Fang
MMS19 localizes to cytoplasmic and nuclear compartments involving in transcription and nucleotide excision repair (NER). However, whether or not MMS19 localizes to mitochondria where it plays a role in maintaining mitochondrial genome stability remains elusive. In this study, we provide the first evidence that MMS19 is localized in the inner membrane of mitochondria and participates in mtDNA oxidative damage repair. MMS19 knockdown led to mitochondrial dysfunctions including decreased mtDNA copy number, diminished mtDNA repair capacity and elevated level of mtDNA common deletion after oxidative stress...
October 16, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29035293/identification-of-z-2-3-diphenylacrylonitrileas-anti-cancer-molecule-in-persian-gulf-sea-cucumber-holothuria-parva
#3
Salimeh Amidi, Zahra Hashemi, Abbasali Motallebi, Melika Nazemi, Hoda Farrokhpayam, Enayatollah Seydi, Jalal Pourahmad
Hepatocellular carcinoma (HCC), also named cancerous hepatoma, is the most common type of malignant neoplasia of the liver. In this research, we screened the Persian Gulf sea cucumber Holothuria parva (H. parva) methanolic sub-fractions for the possible existence of selective toxicity on liver mitochondria isolated from an animal model of HCC. Next, we purified the most active fraction. Thus the structure of the active molecule was identified. HCC was induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) protocol...
October 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29034285/data-on-chow-liver-tissue-and-mitochondrial-fatty-acid-compositions-as-well-as-mitochondrial-proteome-changes-after-feeding-mice-a-western-diet-for-6-24-weeks
#4
Claudia Einer, Simon Hohenester, Ralf Wimmer, Lena Wottke, Renate Artmann, Sabine Schulz, Christian Gosmann, Alisha Simmons, Christin Leitzinger, Carola Eberhagen, Sabine Borchard, Sabine Schmitt, Stefanie M Hauck, Christine von Toerne, Martin Jastroch, Ellen Walheim, Christian Rust, Alexander L Gerbes, Bastian Popper, Doris Mayr, Max Schnurr, Angelika M Vollmar, Gerald Denk, Hans Zischka
The data presented in this article describe the fatty acid composition of chow, liver tissue and isolated liver mitochondria from mice fed for 6-24 weeks with a high caloric western diet (WD) in comparison to control diet (normal diet, ND). The fatty acid composition was measured via gas chromatography flame ionization detection (GC-FID). Moreover, WD-induced mitochondrial protein changes are presented in this work and were analyzed by mass spectrometry (LC-MS/MS). For further interpretation and discussion of the presented data please refer to the research article entitled "Mitochondrial adaptation in steatotic mice" (Einer et al...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29031721/cdkal1-a-type-2-diabetes-susceptibility-gene-regulates-mitochondrial-function-in-adipose-tissue
#5
Colin J Palmer, Raphael J Bruckner, Joao A Paulo, Lawrence Kazak, Jonathan Z Long, Amir I Mina, Zhaoming Deng, Katherine B LeClair, Jessica A Hall, Shangyu Hong, Peter-James H Zushin, Kyle L Smith, Steven P Gygi, Susan Hagen, David E Cohen, Alexander S Banks
OBJECTIVES: Understanding how loci identified by genome wide association studies (GWAS) contribute to pathogenesis requires new mechanistic insights. Variants within CDKAL1 are strongly linked to an increased risk of developing type 2 diabetes and obesity. Investigations in mouse models have focused on the function of Cdkal1 as a tRNA(Lys) modifier and downstream effects of Cdkal1 loss on pro-insulin translational fidelity in pancreatic β-cells. However, Cdkal1 is broadly expressed in other metabolically relevant tissues, including adipose tissue...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29027961/dosis-facit-sanitatem-concentration-dependent-effects-of-resveratrol-on-mitochondria
#6
REVIEW
Corina T Madreiter-Sokolowski, Armin A Sokolowski, Wolfgang F Graier
The naturally occurring polyphenol, resveratrol (RSV), is known for a broad range of actions. These include a positive impact on lifespan and health, but also pro-apoptotic anti-cancer properties. Interestingly, cell culture experiments have revealed a strong impact of RSV on mitochondrial function. The compound was demonstrated to affect mitochondrial respiration, structure and mass of mitochondria as well as mitochondrial membrane potential and, ultimately, mitochondria-associated cell death pathways. Notably, the mitochondrial effects of RSV show a very strict and remarkable concentration dependency: At low concentrations, RSV (<50 μM) fosters cellular antioxidant defense mechanisms, activates AMP-activated protein kinase (AMPK)- and sirtuin 1 (SIRT1)-linked pathways and enhances mitochondrial network formation...
October 13, 2017: Nutrients
https://www.readbyqxmd.com/read/29026190/growth-hormone-secretagogues-hexarelin-and-jmv2894-protect-skeletal-muscle-from-mitochondrial-damages-in-a-rat-model-of-cisplatin-induced-cachexia
#7
Giuseppe Sirago, Elena Conte, Flavio Fracasso, Antonella Cormio, Jean-Alain Fehrentz, Jean Martinez, Clara Musicco, Giulia Maria Camerino, Adriano Fonzino, Laura Rizzi, Antonio Torsello, Angela Maria Serena Lezza, Antonella Liantonio, Palmiro Cantatore, Vito Pesce
Chemotherapy can cause cachexia, which consists of weight loss associated with muscle atrophy. The exact mechanisms underlying this skeletal muscle toxicity are largely unknown and co-therapies to attenuate chemotherapy-induced side effects are lacking. By using a rat model of cisplatin-induced cachexia, we here characterized the mitochondrial homeostasis in tibialis anterior cachectic muscle and evaluated the potential beneficial effects of the growth hormone secretagogues (GHS) hexarelin and JMV2894 in this setting...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024598/effects-of-long-term-exposures-to-low-iron-and-branched-chain-amino-acid-containing-diets-on-aging-skeletal-muscle-of-fisher-344-brown-norway-rats
#8
Yuho Kim, Sok Sambo Men, Chen Liang, Candace N Receno, Tom D Brutsaert, Donna L Korol, Kevin S Heffernan, Keith C DeRuisseau
Aging skeletal muscle displays an altered iron status that may promote oxidative stress and sarcopenia. A low iron (LI) containing diet could reduce muscle iron status and attenuate age-related muscle atrophy. Supplemental branched-chain amino acids (BCAA) may also alleviate sarcopenia by promoting muscle protein synthesis and iron status improvement. This study examined individual and combined effects of LI and BCAA diets on anabolic signaling and iron status in skeletal muscle of aging rats. Twenty-nine-month-old male F344BN rats consumed the following control-base diets: Control + regular iron (35 mg iron/kg) (CR; n = 11); Control + LI (~6 mg iron/kg) (CL; n = 11); 2×BCAA + regular iron (BR; n = 10); and 2×BCAA + LI (BL; n = 12) for 12 weeks...
October 12, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29022919/dcz3301-a-novel-cytotoxic-agent-inhibits-proliferation-in-diffuse-large-b-cell-lymphoma-via-the-stat3-pathway
#9
Xi Sun, Bo Li, Bingqian Xie, Zhijian Xu, Gaomei Chang, Yi Tao, Yong Zhang, Shuaikang Chang, Yingcong Wang, Dandan Yu, Yongsheng Xie, Tingye Li, Houcai Wang, Gege Chen, Liangning Hu, Jun Hou, Yiwen Zhang, Wenqin Xiao, Lu Gao, Jumei Shi, Weiliang Zhu
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, characterized by a rapidly increasing painless mass. A novel compound, DCZ3301, was synthesized that exerted direct cytotoxicity against DLBCL cell lines. The effects of DCZ3301 on DLBCL cells in vitro and in vivo and the associated mechanisms were investigated. DCZ3301 inhibited the viability of DLBCL cell lines, even in the presence of protumorigenesis cytokines. Additionally, the compound induced apoptosis and cell cycle arrest at the G2/M phase by reducing mitochondrial membrane potential...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29019072/mass-spectrometry-based-metabolomics-to-identify-taurine-modified-metabolites-in-heart
#10
Takashi Ito, Koei Okazaki, Daisuke Nakajima, Daisuke Shibata, Shigeru Murakami, Stephen Schaffer
Taurine is an abundant beta-amino acid found in high concentration in mammalian tissues. Taurine possesses many beneficial functions in mammalian cells. There are also a variety of taurine-conjugated products formed between taurine and bile acids, fatty acids, chloramine, mitochondrial tRNA, etc., and some of these have been identified as functional compounds. In the present study, we identified taurine-conjugated metabolites using LC-MS-based metabolome analysis of heart extracts prepared from hearts of wild-type and taurine transporter-knockout (TauTKO) mice, the latter being severely taurine deficient...
October 10, 2017: Amino Acids
https://www.readbyqxmd.com/read/29016348/parp-1-and-parp-2-activity-in-cancer-induced-cachexia-potential-therapeutic-implications
#11
Esther Barreiro, Joaquim Gea
Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28989830/combining-magnetic-resonance-spectroscopy-and-magnetic-resonance-imaging-in-diagnosing-focal-brain-lesions-in-children
#12
Farah Naz, Waseem A Mirza, Nauman Hashmani
Introduction We attempted to find the sensitivity and specificity of various pediatric brain masses in the Pakistani population while keeping histopathology or clinical diagnosis as the gold standard.   Methods This was a retrospective study that was conducted from January 2007 to January 2016. We reviewed the records of 204 patients that presented to the radiology department of Aga Khan University Hospital (AKUH). Out of the 204, 135 pediatric patients in the 0-18 age group with focal brain lesions who underwent magnetic resonance spectroscopy (MRS) and a biopsy or clinical diagnosis were included...
August 4, 2017: Curēus
https://www.readbyqxmd.com/read/28988798/differential-carbonylation-of-proteins-in-end-stage-human-fatty-and-nonfatty-nash
#13
Colin T Shearn, Laura M Saba, James R Roede, David J Orlicky, Alisabeth H Shearn, Dennis R Petersen
OBJECTIVE: In the liver, a contributing factor in the pathogenesis of non-alcoholic fatty liver disease is oxidative stress leading to the accumulation of highly reactive electrophilic α/β unsaturated aldehydes. The objective of this study was to determine if significant differences were evident when evaluating carbonylation in human end-stage fatty nonalcoholic steatohepatitis (fNASH) compared to end-stage nonfatty NASH (nfNASH). METHODS: Using hepatic tissue obtained from healthy humans and patients diagnosed with end stage nfNASH or fNASH, overall carbonylation was assessed by immunohistochemistry (IHC) and LC-MS/MS followed by bioinformatics...
October 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28986697/targeting-mitochondrial-function-and-proteostasis-to-mitigate-dynapenia
#14
REVIEW
Robert V Musci, Karyn L Hamilton, Benjamin F Miller
Traditionally, interventions to treat skeletal muscle aging have largely targeted sarcopenia-the age-related loss of skeletal muscle mass. Dynapenia refers to the age-related loss in skeletal muscle function due to factors outside of muscle mass, which helps to inform treatment strategies for aging skeletal muscle. There is evidence that mechanisms to maintain protein homeostasis and proteostasis, deteriorate with age. One key mechanism to maintain proteostasis is protein turnover, which is an energetically costly process...
October 6, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28986525/non-invasive-assessment-of-hepatic-mitochondrial-metabolism-by-positional-isotopomer-nmr-tracer-analysis-pinta
#15
Rachel J Perry, Liang Peng, Gary W Cline, Gina M Butrico, Yongliang Wang, Xian-Man Zhang, Douglas L Rothman, Kitt Falk Petersen, Gerald I Shulman
Hepatic mitochondria play a central role in the regulation of intermediary metabolism and maintenance of normoglycemia, and there is great interest in assessing rates of hepatic mitochondrial citrate synthase flux (V CS) and pyruvate carboxylase flux (V PC) in vivo. Here, we show that a positional isotopomer NMR tracer analysis (PINTA) method can be used to non-invasively assess rates of V CS and V PC fluxes using a combined NMR/gas chromatography-mass spectrometry analysis of plasma following infusion of [3-(13)C]lactate and glucose tracer...
October 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28979670/quantitative-proteomics-analysis-of-mitochondrial-proteins-in-lung-adenocarcinomas-and-normal-lung-tissue-using-itraq-and-tandem-mass-spectrometry
#16
Wei Li, Xuede Zhang, Wei Wang, Ruiying Sun, Boxuan Liu, Yuefeng Ma, Wei Zhang, Li Ma, Yaofeng Jin, Shuanying Yang
Lung adenocarcinoma is the most common type of lung cancer. Unfortunately, lung adenocarcinoma has a poor prognosis and the pathogenesis remains unclear. Mitochondria are important mediators of tumorigenesis. However, the proteomics profile of lung adenocarcinoma mitochondrial proteins has not been elucidated. In this study, we investigated differences in the mitochondrial protein profiles between lung adenocarcinomas and normal tissue. Laser capture microdissection (LCM) was used to isolate the target cells from lung adenocarcinomas and normal tissue...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28978942/age-related-neurodegenerative-disease-associated-pathways-identified-in-retinal-and-vitreous-proteome-from-human-glaucoma-eyes
#17
Mehdi Mirzaei, Veer B Gupta, Joel M Chick, Todd M Greco, Yunqi Wu, Nitin Chitranshi, Roshana Vander Wall, Eugene Hone, Liting Deng, Yogita Dheer, Mojdeh Abbasi, Mahdie Rezaeian, Nady Braidy, Yuyi You, Ghasem Hosseini Salekdeh, Paul A Haynes, Mark P Molloy, Ralph Martins, Ileana M Cristea, Steven P Gygi, Stuart L Graham, Vivek K Gupta
Glaucoma is a chronic disease that shares many similarities with other neurodegenerative disorders of the central nervous system. This study was designed to evaluate the association between glaucoma and other neurodegenerative disorders by investigating glaucoma-associated protein changes in the retina and vitreous humour. The multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal tissue and vitreous humour fluid collected from glaucoma patients and age-matched controls followed by functional pathway and protein network interaction analysis...
October 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28978813/normal-pancreatic-%C3%AE-cell-function-in-mice-with-rip-cre-mediated-inactivation-of-p62-sqstm1
#18
Akira Honda, Koji Komiya, Akemi Hara, Ayako Fukunaka, Luka Suzuki, Takeshi Miyatsuka, Takeshi Ogihara, Yoshio Fujitani, Hirotaka Watada
Recent studies have suggested that decreased pancreatic β-cell function and mass are common features of patients with type 2 diabetes mellitus. Pancreatic β-cell homeostasis is regulated by various types of signaling molecules and stress responses. Sequestosome 1/p62 (SQSTM1, hereafter referred to as p62) is a ubiquitin-binding adaptor protein involved in cell signaling, oxidative stress, and autophagy. Because p62 appears to play an important role in maintaining mitochondrial quality control, it is possible that the loss of p62 in pancreatic β cells contributes to mitochondrial dysfunction, and thus leading to impaired glucose tolerance...
October 4, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28978719/pharmacological-dual-inhibition-of-tumor-and-tumor-induced-functional-limitations-in-transgenic-model-of-breast-cancer
#19
Ruizhong Wang, Poornima Bhat-Nakshatri, Maria B Padua, Mayuri S Prasad, Manjushree Anjanappa, Max Jacobson, Courtney Finnearty, Victoria Sefcsik, Kyle McElyea, Rachael Redmond, George E Sandusky, Narsimha Penthala, Peter A Crooks, Jianguo Liu, Teresa Zimmers, Harikrishna Nakshatri
Breast cancer progression is associated with systemic effects including functional limitations and sarcopenia without the appearance of overt cachexia. Autocrine/paracrine actions of cytokines/chemokines produced by cancer cells mediate cancer progression and functional limitations. The cytokine-inducible transcription factor NF-κB could be central to this process, as it displays oncogenic functions and is integral to the Pax7:MyoD:Pgc-1β:miR-486 myogenesis axis. We tested this possibility using the MMTV-PyMT transgenic mammary tumor model and the NF-κB inhibitor dimethylaminoparthenolide (DMAPT)...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28978546/subcutaneous-inguinal-white-adipose-tissue-is-responsive-to-but-dispensable-for-the-metabolic-health-benefits-of-exercise
#20
Willem T Peppler, Logan K Townsend, Carly M Knuth, Michelle T Foster, David C Wright
Exercise training has robust effects on subcutaneous inguinal white adipose tissue (iWAT), characterized by a shift to a brown adipose tissue (BAT) like phenotype. Consistent with this, transplantation of exercise-trained iWAT into sedentary rodents activates thermogenesis and improves glucose homeostasis, suggesting that iWAT metabolism may contribute to the beneficial effects of exercise. However, it is yet to be determined if adaptations in iWAT are necessary for the beneficial systemic effects of exercise...
October 3, 2017: American Journal of Physiology. Endocrinology and Metabolism
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