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https://www.readbyqxmd.com/read/29039450/insulin-restores-ucp3-activity-and-decreases-energy-surfeit-to-alleviate-lipotoxicity-in-skeletal-muscle
#1
Wenjuan Tang, Sunyinyan Tang, Hongdong Wang, Zhijuan Ge, Dalong Zhu, Yan Bi
An early insulin regimen ameliorates glucotoxicity but also lipotoxicity in type 2 diabetes; however, the underlying mechanism remains elusive. In the present study, we investigated the role of mitochondria in lipid regulation following early insulin administration in insulin-resistant skeletal muscle cells. Male C57BL/6 mice, fed a high-fat diet (HFD) for 8 weeks, were treated with insulin for 3 weeks, and L6 myotubes cultured with palmitate (PA) for 24 h were incubated with insulin for another 12 h. The results showed that insulin facilitated systemic glucose disposal and attenuated muscular triglyceride accumulation in vivo...
October 2, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29024409/the-natural-agent-rhein-induces-%C3%AE-catenin-degradation-and-tumour-growth-arrest
#2
Shu Liu, Jiao Wang, Ting Shao, Peiying Song, Qingbin Kong, Hui Hua, Ting Luo, Yangfu Jiang
The natural agent rhein is an ananthraquinone derivative of rhubarb, which has anticancer effects. To determine the mechanisms underlying the anticancer effects of rhein, we detected the effect of rhein on several oncoproteins. Here, we show that rhein induces β-catenin degradation in both hepatoma cell HepG2 and cervical cancer cell Hela. Treatment of HepG2 and Hela cells with rhein shortens the half-life of β-catenin. The proteasome inhibitor MG132 blunts the downregulation of β-catenin by rhein. The induction of β-catenin degradation by rhein is dependent on GSK3 but independent of Akt...
October 11, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29021560/the-thiazide-sensitive-sodium-chloride-co-transporter-ncc-is-modulated-by-site-specific-ubiquitylation
#3
Lena L Rosenbaek, Federica Rizzo, Qi Wu, Lorena Rojas-Vega, Gerardo Gamba, Nanna MacAulay, Olivier Staub, Robert A Fenton
The renal sodium chloride cotransporter, NCC, in the distal convoluted tubule is important for maintaining body Na(+) and K(+) homeostasis. Endogenous NCC is highly ubiquitylated, but the role of individual ubiquitylation sites is not established. Here, we assessed the role of 10 ubiquitylation sites for NCC function. Transient transfections of HEK293 cells with human wildtype (WT) NCC or various K to R mutants identified greater membrane abundance for K706R, K828R and K909R mutants. Relative to WT-NCC, stable tetracycline inducible MDCKI cell lines expressing K706R, K828R and K909R mutants had significantly higher total and phosphorylated NCC levels at the apical plasma membrane under basal conditions...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28968276/sevoflurane-acts-on-ubiquitination-proteasome-pathway-to-reduce-postsynaptic-density-95-protein-levels-in-young-mice
#4
Han Lu, Ning Liufu, Yuanlin Dong, Guanghong Xu, Yiying Zhang, Liqi Shu, Sulpicio G Soriano, Hui Zheng, Buwei Yu, Zhongcong Xie
BACKGROUND: Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane, a commonly used anesthetic in children, has been reported to decrease levels of postsynaptic density 95 protein. However, the upstream mechanisms and downstream consequences of the sevoflurane-induced reduction in postsynaptic density 95 protein levels remains largely unknown. We therefore set out to assess whether sevoflurane acts on ubiquitination-proteasome pathway to facilitate postsynaptic density 95 protein degradation...
October 2, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28957379/involvement-of-parkin-in-the-ubiquitin-proteasome-system-mediated-degradation-of-n-type-voltage-gated-ca2-channels
#5
Lizbeth Grimaldo, Alejandro Sandoval, Edgar Garza-López, Ricardo Felix
N-type calcium (CaV2.2) channels are widely expressed in the brain and the peripheral nervous system, where they play important roles in the regulation of transmitter release. Although CaV2.2 channel expression levels are precisely regulated, presently little is known regarding the molecules that mediate its synthesis and degradation. Previously, by using a combination of biochemical and functional analyses, we showed that the complex formed by the light chain 1 of the microtubule-associated protein 1B (LC1-MAP1B) and the ubiquitin-proteasome system (UPS) E2 enzyme UBE2L3, may interact with the CaV2...
2017: PloS One
https://www.readbyqxmd.com/read/28955790/application-of-a-novel-hibit-peptide-tag-for-monitoring-atf4-protein-expression-in-neuro2a-cells
#6
Kentaro Oh-Hashi, Eri Furuta, Keito Fujimura, Yoko Hirata
A split NanoLuc assay system consisting of two fragments, large N-terminal and small C-terminal regions (NanoBiT), was developed to investigate protein-protein interactions within living cells. Interestingly, the replacement of five amino acids among 11 C-terminal amino acids dramatically increased affinity against the large N-terminal fragment, LgBiT, and the complex had NanoLuc luciferase activity. In this study, we first applied this small fragment, HiBiT, to elucidate the expression of ATF4 protein by transient overexpression of HiBiT-tagged ATF4...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28951443/converging-sumo-and-ubiquitin-signaling-improved-methodology-identifies-co-modified-target-proteins
#7
Sabine A G Cuijpers, Edwin Willemstein, Alfred C O Vertegaal
Post translational protein modifications (PTMs) including small chemical groups and small proteins, belonging to the ubiquitin family, are essential for virtually all cellular processes. In addition to modification by a single PTM, proteins can be modified by a combination of different modifiers, which are able to influence each other. Since little is known about crosstalk between different ubiquitin family members, we developed an improved method enabling identification of co-modified proteins on a system-wide level using mass spectrometry...
September 26, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28946669/blocking-of-the-ubiquitin-proteasome-system-prevents-inflammation-induced-bone-loss-by-accelerating-m-csf-receptor-c-fms-degradation-in-osteoclast-differentiation
#8
Kyunghee Lee, Mi Yeong Kim, Heejin Ahn, Han-Sung Kim, Hong-In Shin, Daewon Jeong
Anti-osteoporotic activity of a blocker of the ubiquitin-proteasome system, bortezomib, has known to be achieved by directly opposed action in increased bone formation by osteoblasts and in decreased bone destruction by osteoclasts. However, the mechanisms underlying the proteasome blocker inhibition of osteoclast differentiation and function are not fully understood. Here, we observed that proteasome inhibitors, such as MG132 and bortezomib, in osteoclasts accelerated the degradation of c-Fms, a cognate receptor of macrophage colony-stimulating factor (M-CSF), and did not affect the amount of receptor activator of nuclear factor kappa-B (RANK), a receptor of receptor activator of nuclear factor kappa-B ligand (RANKL)...
September 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28942144/microgravity-influences-maintenance-of-the-human-muscle-stem-progenitor-cell-pool
#9
Tohru Hosoyama, Shunji Ichida, Masatsugu Kanno, Reiichi Ishihara, Toshikatsu Hatashima, Koji Ueno, Kimikazu Hamano
Microgravity induces skeletal muscle atrophy; however, the underlying mechanism is not clarified. In particular, the influence of microgravity on human skeletal muscle stem/progenitor cells (SMPCs) is not well understood. In this study, we used induced pluripotent stem cell-derived human SMPCs to investigate the effect of microgravity on maintenance of the stem/progenitor cell pool. Human SMPCs were induced by free-floating spherical aggregation culture, and derivatized-SMPC spheres were maintained in a microgravity condition (10(-3) G) for 2 weeks using a clinostat rotation system...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28941726/a-role-of-bag3-in-regulating-snca-%C3%AE-synuclein-clearance-via-selective-macroautophagy
#10
Yu-Lan Cao, Ya-Ping Yang, Cheng-Jie Mao, Xiao-Qi Zhang, Chen-Tao Wang, Jing Yang, Dong-Jun Lv, Fen Wang, Li-Fang Hu, Chun-Feng Liu
Many studies reveal that BAG3 plays a critical role in the regulation of protein degradation via macroautophagy. However, it remains unknown whether BAG3 affects the quality control of α-synuclein (SNCA), a Parkinson's disease-related protein. In this study, we demonstrated the increases of BAG3 expression in the ventral midbrain of SNCA(A53T) transgenic mice and also in MG132-treated PC12 cells overexpressing wild-type SNCA (SNCA(WT)-PC12). Moreover, we showed that BAG3 overexpression was sufficient to enhance the autophagy activity while knockdown of Bag3 reduced it in SNCA(WT)-PC12 cells...
September 1, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28939105/protein-kinase-c-eta-regulates-mcl-1-level-via-erk1
#11
Deepanwita Pal, Alakananda Basu
Protein kinase C (PKC)-eta (PKCη) is a member of the novel category of PKC family. It is overexpressed in breast cancer and was shown to inhibit apoptosis and contribute to chemoresistance. Since the anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance, we investigated if PKCη regulates Mcl-1 level. Silencing of PKCη decreased Mcl-1 in several breast cancer cells, including MCF-7 and T47D cells. PKCη depletion had no effect on MCL1 mRNA but the decrease in Mcl-1 by PKCη knockdown was blocked by proteasomal inhibitors, such as MG132 and lactacystin...
September 20, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28915612/the-roles-of-ing5-in-gliomas-a-good-marker-for-tumorigenesis-and-a-potential-target-for-gene-therapy
#12
Shuang Zhao, Zhi-Juan Zhao, Hao-Yu He, Ji-Cheng Wu, Xiao-Qing Ding, Lei Yang, Ning Jia, Zhi-Jie Li, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of ING5 on glioma cells, we overexpressed it in U87 cells, and examined the phenotypes and their relevant molecules. It was found that ING5 overexpression suppressed proliferation, energy metabolism, migration, invasion, and induced G2/M arrest, apoptosis, dedifferentiation, senescence, mesenchymal- epithelial transition and chemoresistance to cisplatin, MG132, paclitaxel and SAHA in U87 cells. There appeared a lower expression of N-cadherin, Twist, Slug, Zeb1, Zeb2, Snail, Ac-H3, Ac-H4, Cdc2, Cdk4 and XIAP, but a higher expression of Claudin 1, Histones 3 and 4, p21, p53, Bax, β-catenin, PI3K, Akt, and p-Akt in ING5 transfectants...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901514/multimodal-actions-of-the-phytochemical-sulforaphane-suppress-both-ar-and-ar-v7-in-22rv1-cells-advocating-a-potent-pharmaceutical-combination-against-castration-resistant-prostate-cancer
#13
Namrata Khurana, Hogyoung Kim, Partha K Chandra, Sudha Talwar, Pankaj Sharma, Asim B Abdel-Mageed, Suresh C Sikka, Debasis Mondal
Prostate cancer (PCa) cells expressing full-length androgen receptor (AR-FL) are susceptible to androgen deprivation therapy (ADT). However, outgrowth of castration-resistant prostate cancer (CRPC) can occur due to the expression of constitutively active (ligand-independent) AR splice variants, particularly AR-V7. We previously demonstrated that sulforaphane (SFN), an isothiocyanate phytochemical, can decrease AR-FL levels in the PCa cell lines, LNCaP and C4-2B. Here, we examined the efficacy of SFN in targeting both AR-FL and AR-V7 in the CRPC cell line, CWR22Rv1 (22Rv1)...
November 2017: Oncology Reports
https://www.readbyqxmd.com/read/28900483/sulforaphane-induced-apoptosis-via-promotion-of-mitochondrial-fusion-and-erk1-2-mediated-26s-proteasome-degradation-of-novel-pro-survival-bim-and-upregulation-of-bax-in-human-non-small-cell-lung-cancer-cells
#14
Yang Geng, Yan Zhou, Sai Wu, Yabin Hu, Kai Lin, Yalin Wang, Zhongnan Zheng, Wei Wu
Previous studies in our laboratory showed that sulforaphane (SFN) induced apoptosis by sustained activation of extracellular regulated protein kinases 1/2 (ERK1/2). However, the underlying mechanisms associated with SFN-induced apoptosis and downstream cascades which are modulated by ERK1/2 were not elucidated. Herein we demonstrated for the first time that alteration of mitochondrial dynamics contributed to SFN-induced apoptosis in human non-small cell lung cancer (NSCLC) cells. Reports showed that protein Bim not only induced apoptosis but also promoted proliferation under certain circumstances...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28893904/anthrax-lethal-toxin-rapidly-reduces-c-jun-levels-by-inhibiting-c-jun-gene-transcription-and-promoting-c-jun-protein-degradation
#15
Weiming Ouyang, Pengfei Guo, Hui Fang, David M Frucht
Anthrax is a life threatening disease caused by infection with Bacillus anthracis, which expresses lethal factor and the receptor-binding protective antigen. These two proteins combine to form anthrax lethal toxin (LT), whose proximal targets are mitogen activated kinase kinases (MKKs). However, the downstream mediators of LT toxicity remain elusive. We herein report that LT exposure rapidly reduces the levels of cJun, a key regulator of cell proliferation and survival. Blockade of proteasome dependent protein degradation with the 26S proteasome inhibitor MG132 largely restored cJun protein levels, suggesting that LT promotes degradation of cJun protein...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28870200/anticancer-activity-of-calyx-of-diospyros-kaki-thunb-through-downregulation-of-cyclin-d1-via-inducing-proteasomal-degradation-and-transcriptional-inhibition-in-human-colorectal-cancer-cells
#16
Su Bin Park, Gwang Hun Park, Hun Min Song, Ho-Jun Son, Yurry Um, Hyun-Seok Kim, Jin Boo Jeong
BACKGROUND: Although it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. METHODS: Anti-cell proliferative effect of 70% ethanol extracts from the calyx of Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively...
September 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28861610/inhibitors-of-the-proteasome-stimulate-the-epithelial-sodium-channel-enac-through-sgk1-and-mimic-the-effect-of-aldosterone
#17
Morag K Mansley, Christoph Korbmacher, Marko Bertog
The epithelial sodium channel (ENaC) marks the tightly regulated, rate-limiting step of sodium re-absorption in the aldosterone-sensitive distal nephron (ASDN). Stimulation of ENaC activity by aldosterone involves the serum and glucocorticoid-induced kinase 1 (SGK1) and is mediated via complex mechanisms including inhibition of channel retrieval. Retrieved channels may be recycled or degraded, e.g. by the proteasomal pathway. The aim of the present study was to investigate whether inhibitors of the proteasome affect ENaC activity and surface expression, and to explore a possible involvement of SGK1...
August 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28860152/proteasome-inhibitor-bortezomib-is-a-novel-therapeutic-agent-for-focal-radiation-induced-osteoporosis
#18
Abhishek Chandra, Luqiang Wang, Tiffany Young, Leilei Zhong, Wei-Ju Tseng, Michael A Levine, Keith Cengel, X Sherry Liu, Yejia Zhang, Robert J Pignolo, Ling Qin
Bone atrophy and its related fragility fractures are frequent, late side effects of radiotherapy in cancer survivors and have a detrimental impact on their quality of life. In another study, we showed that parathyroid hormone 1-34 and anti-sclerostin antibody attenuates radiation-induced bone damage by accelerating DNA repair in osteoblasts. DNA damage responses are partially regulated by the ubiquitin proteasome pathway. In the current study, we examined whether proteasome inhibitors have similar bone-protective effects against radiation damage...
August 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28859856/gastrin-induces-nuclear-export-and-proteasome-degradation-of-menin-in-enteric-glial-cells
#19
Sinju Sundaresan, Cameron A Meininger, Anthony J Kang, Amanda L Photenhauer, Michael M Hayes, Nirakar Sahoo, Jolanta Grembecka, Tomasz Cierpicki, Lin Ding, Thomas J Giordano, Tobias Else, David J Madrigal, Malcolm J Low, Fiona Campbell, Ann-Marie Baker, Haoxing Xu, Nicholas A Wright, Juanita L Merchant
BACKGROUND & AIMS: The multiple endocrine neoplasia, type 1 (MEN1) locus encodes the nuclear protein and tumor suppressor menin. MEN1 mutations frequently cause neuroendocrine tumors (NETs) such as gastrinomas, characterized by their predominant duodenal location and local metastasis at time of diagnosis. Diffuse gastrin cell hyperplasia precedes the appearance of MEN1 gastrinomas, which develop within submucosal Brunner's glands. We investigated how menin regulates expression of the gastrin gene and induces generation of submucosal gastrin-expressing cell hyperplasia...
August 28, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28859215/1-acetoxychavicol-acetate-increases-proteasome-activity-by-activating-camp-pka-signaling
#20
Keisuke Yaku, Isao Matsui-Yuasa, Akiko Kojima-Yuasa
Protein degradation systems are critical pathways for the maintenance of protein homeostasis. The age-dependent attenuation of the proteasome activity contributes to age-related neurodegenerative processes. The molecule 1'-acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Zingiberaceae plants, such as Languas galangal and Alpinia galangal, and exhibits anti-carcinogenic effects. Recently, we have shown that ACA protected the age-related learning and memory impairments in senescence-accelerated mice and maintained cognitive performance...
August 31, 2017: Planta Medica
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