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Yuntao Ji, Meixia Cao, Jia Liu, Yanfei Chen, Xiaoli Li, Jing Zhao, Changqing Qu
Aim: Adipogenesis is characterized by a strong interdependence between cell shape, cytoskeletal organization, and the onset of adipogenic gene expression. Here we investigated the role of the RhoA/ROCK pathway in adipogenesis. Result: High RhoA activity in the cell line C3H10T1/2 were generated (Named RhoA14V cells). Treatment of RhoA14V cells with Shield 1 following their differentiation into adipocytes resulted in the appearance of thick cortical actin filaments, and increased mRNA expression levels of RhoA, ROCK, p-MYPT1 and p-MLC, while PPARγ mRNA decreased...
December 2017: Saudi Journal of Biological Sciences
Hironao Nakayama, Tomohisa Sakaue, Masashi Maekawa, Ayako Fujisaki, Shigeki Higashiyama
A disintegrin and metalloproteinase (ADAM) family are crucial enzymes for ectodomain shedding of multiple substrates and are involved in diverse biologic and pathologic processes. However, the molecular mechanism underlying substrate selectivity of ADAMs is poorly understood. In this study, we observed that disruption of actin polymerization by pharmacological inhibitors, latrunculin A (LatA) and cytochalasin D (CyD), induced ectodomain shedding of epidermal growth factor (EGF) family ligands. Induced shedding activity by LatA or CyD was suppressed by a metalloprotease inhibitor KB-R7785, indicating that ADAMs-mediated shedding is tightly controlled by actin cytoskeleton...
March 14, 2018: Biochemical and Biophysical Research Communications
Claudia Kruger, Susan J Burke, J Jason Collier, Trang-Tiffany Nguyen, J Michael Salbaum, Krisztian Stadler
Early podocyte loss is characteristic of chronic kidney diseases (CKD) in obesity and diabetes. Since treatments for hyperglycemia and hypertension do not prevent podocyte loss, there must be additional factors causing podocyte depletion. The role of oxidative stress has been implicated in CKD but it is not known how exactly free radicals affect podocyte physiology. To assess this relationship, we investigated the effects of lipid radicals on podocytes, as lipid peroxidation is a major form of oxidative stress in diabetes...
March 6, 2018: Redox Biology
Teklab Gebregiworgis, Christopher Boyd Marshall, Tadateru Nishikawa, Nikolina Radulovich, María-José Sandi, Zhenhao Fang, Robert Rottapel, Ming-Sound Tsao, Mitsuhiko Ikura
Small GTPases (sGTPases) are critical switch-like regulators that mediate several important cellular functions and are often mutated in human cancers. They are activated by guanine nucleotide exchange factors (GEFs), which specifically catalyze the exchange of GTP for GDP. GEFs coordinate signaling networks in normal cells, and are frequently deregulated in cancers. sGTPase signaling pathways are complex and interconnected; however, most GEF assays do not reveal such complexity. In this communication, we describe the development of a unique real-time NMR-based multiplexed GEF assay that employs distinct isotopic labeling schemes for each sGTPase protein to enable simultaneous observation of six proteins of interest...
March 15, 2018: Journal of the American Chemical Society
Heather L Lehman, Michal Kidacki, Joshua I Warrick, Douglas B Stairs
Four out of five patients diagnosed with esophageal squamous cell carcinoma (ESCC) will die within five years. This is primarily a result of the aggressive invasive potential of the disease. Our research is focused on the interplay between tumor suppressors and oncogenes in the invasive process. Specifically, EGFR and p120-catenin (p120ctn) are commonly dysregulated genes that are indicative of poor prognosis in ESCC. In a previous study we demonstrated that in our 3D organotypic culture model, only when EGFR overexpression is combined with p120ctn inactivation do the cells transform and invade - as opposed to either event alone...
February 16, 2018: Oncotarget
Sheng-Yong Luo, Qing-Hua Xu, Gong Peng, Zhi-Wu Chen
Objectives: Total flavones from Rhododendron simsii Planch. (TFR) are the effective part extracted from the flowers of Rhododendron simsii Planch. and have obvious protective effects against cerebral ischemic or myocardial injuries in rabbits and rats. However, their mechanism of cardioprotection is still unrevealed. Therefore, the present study was designed to investigate the effect of TFR on myocardial I/R injury and the underlying mechanism. Methods: TFR groups were treated by gavage once a day for 3 days at a dose of 20, 40, and 80 mg/kg, respectively, and then the model of myocardial I/R injury was established...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Alexis Bonfim-Melo, Éden R Ferreira, Renato A Mortara
This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups...
2018: Frontiers in Microbiology
Julien Daubriac, Shiwei Han, Jelena Grahovac, Eve Smith, Abdel Hosein, Marguerite Buchanan, Mark Basik, Yves Boucher
Carcinoma-associated fibroblasts (CAFs) can remodel the extracellular matrix to promote cancer cell invasion, but the paracrine signaling between CAFs and cancer cells that regulates tumor cell migration remains to be identified. To determine how the interaction between CAFs and cancer cells modulates the invasiveness of cancer cells, we developed a 3-dimensional co-culture model composed of breast cancer (BC) MDA-MB-231 cell spheroids embedded in a collagen gel with and without CAFs. We found that the crosstalk between CAFs and cancer cells promotes invasion by stimulating the scattering of MDA-MB-231 cells, which was dependent on RhoA/ROCK/phospho MLC signaling in cancer cells but independent of RhoA in CAFs...
February 13, 2018: Oncotarget
Richard T Amison, Shirin Jamshidi, Khondaker M Rahman, Clive P Page, Simon C Pitchford
Platelet P2Y1 receptor signaling via RhoGTPases is necessary for platelet-dependent leukocyte recruitment, where no platelet aggregation is observed. We investigated signaling cascades involved in distinct P2Y1 -dependent platelet activities in vitro, using specific inhibitors for phospholipase C (PLC) (U73122, to inhibit the canonical pathway), and RhoGTPases: Rac1 (NSC23766) and RhoA (ROCK inhibitor GSK429286). Human platelet rich plasma (for platelet aggregation) or isolated washed platelets (for chemotaxis assays) was treated with U73122, GSK429286 or NSC23766 prior to stimulation with adenosine diphosphate (ADP) or the P2Y1 specific agonist MRS2365...
March 10, 2018: European Journal of Pharmacology
Gamal Badr, Halise Inci Gul, Cem Yamali, Amal A M Mohamed, Badr M Badr, Mustafa Gul, Ahmad Abo Markeb, Nagwa Abo El-Maali
Recent developments in the literature have demonstrated that curcumin exhibit antioxidant properties supporting its anti-inflammatory, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Despite the valuable findings of curcumin against different cancer cells, the clinical use of curcumin in cancer treatment is limited due to its extremely low aqueous solubility and instability, which lead to poor in vivo bioavailability and limited therapeutic effects. We therefore focused in the present study to evaluate the anti-tumor potential of curcumin analogues on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10)...
March 7, 2018: Bioorganic Chemistry
Sawana Singkhorn, Mayuree H Tantisira, Supita Tanasawet, Pilaiwanwadee Hutamekalin, Tulaporn Wongtawatchai, Wanida Sukketsiri
Centella asiatica is widely considered the most important medicinal plant for treating and relieving skin diseases. Recently developed standardized extract of Centella asiatica ECa 233 has demonstrated positive effects on wound healing of incision and burn wound in rats. However, knowledge associated with wound healing mechanism of ECa 233 was scare. Therefore, this study aimed to investigate the effect and underlying molecular mechanisms of ECa 233 on the migration of a human keratinocyte cell line (HaCaT) using scratch wound healing assay...
March 13, 2018: Phytotherapy Research: PTR
Yuan Dai, Weijia Luo, Jiang Chang
Rho kinases (ROCKs) are the first discovered RhoA effectors that are now widely known for their effects on actin organization. Recent studies have shown that ROCKs play important roles in cardiac physiology. Abnormal activation of ROCKs participate in multiple cardiovascular pathological processes, including cardiac hypertrophy, apoptosis, fibrosis, systemic hypertension, and pulmonary hypertension. ROCK inhibitors, fasudil and statins, have shown beneficial cardiovascular effects in many animal studies, clinical trials, and applications...
February 2018: Current Opinion in Physiology
Marina Leone, Gentian Musa, Felix Benedikt Engel
Aims: After birth mammalian cardiomyocytes initiate a last cell cycle which results in binucleation due to cytokinesis failure. Despite its importance for cardiac regenerative therapies, this process is poorly understood. Here, we aimed at a better understanding of the difference between cardiomyocyte proliferation and binucleation, and providing a new tool to distinguish these two processes. Methods and Results: Monitoring of cell division by time-lapse imaging revealed that rat cardiomyocyte binucleation stems from a failure to properly ingress the cleavage furrow...
March 7, 2018: Cardiovascular Research
Lifeng Qin, Jinmei Qin, Xiumei Zhen, Qian Yang, Liyi Huang
The C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12/ CXCR4) biological axis plays an important role in the pathogenesis of liver fibrosis. Curcumin is known to have an anti-fibrosis effect, but the specific mechanism needs to be elucidated. There is currently no evidence illustrating a connection between curcumin and the CXCL12/CXCR4 axis in liver fibrosis. Here, we investigated the contribution of curcumin on CXCL12/ CXCR4 biological axis in liver fibrosis. Our results showed that curcumin remarkably improved hepatic function and liver fibrosis, and the effects are similar as silymarin...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Laura Pietrovito, Angela Leo, Valentina Gori, Matteo Lulli, Matteo Parri, Valentina Becherucci, Luisa Piccini, Franco Bambi, Maria Letizia Taddei, Paola Chiarugi
There is growing evidence to suggest that bone marrow-derived mesenchymal stem cells (BM-MSCs) are key players in tumor stroma. Here, we investigated the cross-talk between BM-MSCs and osteosarcoma (OS) cells. We revealed a strong tropism of BM-MSCs towards these tumor cells, and identified MCP-1, GRO-α and TGF-β1 as pivotal factors for BM-MSC chemotaxis. Once in contact with OS cells, BM-MSCs transdifferentiate into cancer-associated fibroblasts, further increasing MCP-1, GRO-α, IL-6 and IL-8 levels in the tumor microenvironment...
March 8, 2018: Molecular Oncology
Anne Müsch
The vertebrate liver presents a fascinating case study for how cell form is optimized for function. To execute its duties the liver assembles two distinct lumen-forming epithelial phenotypes: Firstly, cords with a branched, capillary-like luminal network formed between hepatocytes (bile canaliculi); and secondly, tubular ducts formed by biliary epithelial cells arranged around a central cavity and connected to the bile canaliculi. How these remarkably different epithelial polarity phenotypes are generated and joined into a contiguous luminal network are major unresolved questions...
March 2, 2018: Current Opinion in Cell Biology
Abdullah A Mosabbir, Anam Qudrat, Kevin Truong
As monoclonal antibodies have two epitopes for their target ligand, they should theoretically dimerize target receptors upon binding. In particular, the dimerization of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) stimulates early events occurring within minutes (e.g. Ca2+ signal generation) and late events occurring over hours and days (e.g. cell migration in angiogenesis). Although studies have noted that antibodies targeting VEGFR2 (anti-VEGFR2) inhibited cell migration in angiogenesis, we show in this paper that an anti-VEGFR2 stimulus nevertheless triggered a Ca2+ signal in VEGFR2 expressing cells...
March 5, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Eirini Nomikou, Melina Livitsanou, Christos Stournaras, Dimitris Kardassis
Rho GTPases are highly conserved proteins that play critical roles in many cellular processes including actin dynamics, vesicular trafficking, gene transcription, cell-cycle progression, and cell adhesion. The main mode of regulation of Rho GTPases is through guanine nucleotide binding (cycling between an active GTP-bound form and an inactive GDP-bound form), but transcriptional, post-transcriptional, and post-translational modes of Rho regulation have also been described. In the present review, we summarize recent progress on the mechanisms that control the expression of the three members of the Rho-like subfamily (RhoA, RhoB, and RhoC) at the level of gene transcription as well as their post-transcriptional regulation by microRNAs...
March 2, 2018: Cellular and Molecular Life Sciences: CMLS
(no author information available yet)
No abstract text is available yet for this article.
March 2, 2018: Journal of Cell Science
Kazunori Nishimura, Sumiko Watanabe, Tsunehisa Kaku, Setsuo Sugishima
Serum starvation induces binucleation in HeLa cells, but the effects of serum starvation on mitosis and the significance of binucleation remain unknown. We investigated the effect of serum starvation on mitosis and analyzed the growth of binucleated cells. The frequency of binucleation caused by cytokinesis failure in DMEM without FBS (0% medium) was higher than that in DMEM with FBS (10% medium). In 0% medium, the metaphase spindle location was off-center, and RhoA localization significantly lacked symmetry...
March 2, 2018: Bioscience, Biotechnology, and Biochemistry
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