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Akt platelet

Maryam Dastan, Nowruz Najafzadeh, Ali Abedelahi, Mohammadreza Sarvi, Ali Niapour
Minoxidil and human platelet lysate (HPL) are commonly used to treat patients with hair loss. However, the roles of HPL versus minoxidil in hair follicle biology largely remain unknown. Here, we hypothesized that bulge and dermal papilla (DP) cells may express specific genes, including Kras, Erk, Akt, Shh and β-catenin after exposure to minoxidil or HPL. The mouse hair follicles were isolated on day 10 after depilation and bulge or DP regions were dissected. The bulge and DP cells were cultured for 14days in DMEM/F12 medium...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Kyungho Kim, Jing Li, Andrew Barazia, Alan Tseng, Seock-Won Youn, Giovanni Abbadessa, Yi Yu, Brian Schwartz, Robert K Andrews, Victor R Gordeuk, Jaehyung Cho
Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target for thromboinflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in Phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50-500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets...
October 6, 2016: Haematologica
Xie Ge, Si-Yu Chen, Mei Liu, Ting-Ming Liang, Chang Liu
Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in‑stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet‑derived growth factor‑BB (PDGF‑BB) stimulation...
October 5, 2016: Molecular Medicine Reports
Islam Osman, Ninu Poulose, Vadivel Ganapathy, Lakshman Segar
Insulin resistance is associated with accelerated atherosclerosis. Although high fructose is known to induce insulin resistance, it remains unclear as to how fructose regulates insulin receptor signaling and proliferative phenotype in vascular smooth muscle cells (VSMCs), which play a major role in atherosclerosis. Using human aortic VSMCs, we investigated the effects of high fructose treatment on insulin receptor substrate-1 (IRS-1) serine phosphorylation, insulin versus platelet-derived growth factor (PDGF)-induced phosphorylation of Akt, S6 ribosomal protein, and extracellular signal-regulated kinase (ERK), and cell cycle proteins...
October 8, 2016: European Journal of Pharmacology
Britt Van Aelst, Rosalie Devloo, Pierre Zach Eacutee, Ruben t'Kindt, Koen Sandra, Philippe Vandekerckhove, Veerle Compernolle, Hendrik B Feys
Psoralen and ultraviolet A light (PUVA) is used to kill pathogens in blood products and as a treatment of aberrant cell proliferation in dermatitis, cutaneous T-cell lymphoma and graft-versus-host-disease (GVHD). DNA damage is well described, but the direct effects of PUVA on cell signal transduction are poorly understood. Because platelets are anucleate and contain archetypal signal transduction machinery these are ideally suited to address this. Lipidomics on platelet membrane extracts showed that psoralen forms adducts with unsaturated carbon bonds of fatty acyls in all major phospholipid classes after PUVA...
September 29, 2016: Journal of Biological Chemistry
Jie Ma, Yuanyuan Zhao, Li Sun, Xiaochun Sun, Xiaosu Zhao, Xiaoxian Sun, Hui Qian, Wenrong Xu, Wei Zhu
: : We have previously demonstrated the cardioprotective effects of exosomes derived from mesenchymal stem cells (MSCs). It is well-known that the activation of Akt is involved in stem cell-induced cardioprotection. In the present study, we investigated whether exosomes released from Akt-overexpressing MSCs showed a beneficial effect on cardioprotection and angiogenesis. MSCs were collected from human umbilical cord (hucMSCs), and Akt was transfected into hucMSCs (Akt-hucMSCs) by using an adenovirus transfection system...
September 22, 2016: Stem Cells Translational Medicine
Aditya K Gupta, Jessie Carviel
BACKGROUND: Platelet-rich plasma (PRP) therapy is a novel procedure used to treat androgenetic alopecia (AGA). OBJECTIVE: Propose a mechanism of action of PRP therapy for AGA. METHODS AND MATERIALS: A thorough literature search including PRP research for AGA therapy as well as PRP research in other areas of medicine was conducted. RESULTS: A mechanistic model for the action of PRP on the hair follicle was created. CONCLUSION: Platelet-rich plasma therapy stimulates hair growth through the promotion of vascularization and angiogenesis, as well as encourages hair follicles to enter and extend the duration of the anagen phase of the growth cycle...
September 14, 2016: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
Dian-Qi Li, Qi-Long Wan, Janak L Pathak, Zu-Bing Li
Enhanced osteoclast formation increases bone resorption, which triggers bone remodeling. Platelet-derived growth factor BB (PDGF-BB) enhances precursor cell homing, angiogenesis, and bone healing, and thereby could also treat osteoporosis. However, the effect of PDGF-BB on osteoclast formation is not fully understood. We investigated whether exogenous recombinant PDGF-BB directly affects osteoclast formation and osteoclast precursor cell chemotaxis. The murine monocyte-macrophage cell line RAW264.7 and bone-marrow-derived macrophages were cultured with recombinant mouse PDGF-BB with or without a platelet-derived growth factor receptor β inhibitor (AG-1295) or a Janus kinase 2 inhibitor (AG-490) to analyze the effect on osteoclastogenesis in vitro...
September 14, 2016: Journal of Bone and Mineral Metabolism
Romana Moench, Tanja Grimmig, Vinicius Kannen, Sudipta Tripathi, Marc Faber, Eva-Maria Moll, Anil Chandraker, Reinhard Lissner, Christoph-Thomas Germer, Ana Maria Waaga-Gasser, Martin Gasser
Platelet-derived growth factor (PDGF) and signaling via its receptors plays a crucial role in tumor cell proliferation and thus may represent an attractive target besides VEGF/EGFR-based antibody therapies. In this study we analyzed the influence of PDGF in colorectal cancer. PDGF was expressed intensively in early and even more intensively in late stage primary CRCs. Like VEGF, PDGF enhanced human colon cancer proliferation, and increased oxidative glycolytic activity, and activated HIF1α and c-Myc in vitro...
September 8, 2016: Oncotarget
Maria Concetta Olianas, Simona Dedoni, Pier Luigi Onali
Antidepressants have been shown to affect glial cell functions and intracellular signalling through mechanisms still not completely understood. In the present study, we provide evidence that in glial cells the lysophosphatidic acid (LPA) receptor LPA1 mediates antidepressant-induced growth factor receptor transactivation, ERK1/2 signalling, and protection from oxidative stress. Thus, in C6 glioma cells and rat cortical astrocytes ERK1/2 activation induced by either amitriptyline or mianserin was antagonized by Ki16425 and VPC 12249 (S), which block LPA1 and LPA3 receptors, and by AM966, which selectively blocks LPA1 Cell depletion of LPA1 with siRNA treatment markedly reduced antidepressant- and LPA-induced ERK1/2 phosphorylation...
September 7, 2016: Journal of Pharmacology and Experimental Therapeutics
Lu Liu, Yilin Pan, Yang Song, Xiaofan Su, Rui Ke, Lan Yang, Li Gao, Manxiang Li
The aims of the present study were to examine the effect of adenosine monophosphate-activated protein kinase (AMPK) activation on airway smooth muscle cells (ASMCs) proliferation and to address its potential mechanisms. Platelet derived growth factor (PDGF) activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, and this in turn up-regulated S-phase kinase-associated protein 2 (Skp2) and consequently reduced cyclin dependent kinase inhibitor 1B (p27) leading to ASMCs proliferation...
September 4, 2016: European Journal of Pharmacology
Ilaria Canobbio, Caterina Visconte, Barbara Oliviero, Gianni Guidetti, Marta Zarà, Giordano Pula, Mauro Torti
Vascular dysfunctions and Alzheimer's disease show significant similarities and overlaps. Cardiovascular risk factors (hypercholesterolemia, hypertension, obesity, atherosclerosis and diabetes) increase the risk of vascular dementia and Alzheimer's disease. Conversely, Alzheimer's patients have considerably increased predisposition of ischemic and hemorrhagic strokes. Platelets are major players in haemostasis and thrombosis and are involved in inflammation. We have investigated morphology and function of platelets in 3xTg-AD animals, a consolidate murine model for Alzheimer's disease...
December 2016: Cellular Signalling
Xue Zhao, Jun Hao, Huijun Duan, Zanhua Rong, Fan Li
In the present study, the effect and mechanism of periostin on renal proliferation and extracellular matrix accumulation of lupus mice were investigated. MRL/lpr mice, known as lupus mice, were revealed to show enhanced periostin, proliferating cell nuclear antigen (PCNA), and extracellular matrix accumulation in the kidney accompanied by increased serum platelet-derived growth factor (PDGF). Again, cultured mouse mesangial cells (MMCs) were treated with PDGF, then periostin, and PCNA and secreted fibronectin were detected...
September 2, 2016: Experimental Biology and Medicine
Danyang Liu, Yonglong Zhang, Yingze Wei, Guoyuan Liu, Yufeng Liu, Qiongmei Gao, Liping Zou, Wenjiao Zeng, Nong Zhang
Nuclear factor erythroid-2-related factor 2 (Nrf2), a master transcription factor in the antioxidant response, has been found to be ubiquitously expressed in various cancer cells and in the regulation tumor proliferation, invasion, and chemoresistance activities. The regulatory roles of Nrf2 in controlling Hepatocellular carcinoma (HCC) progression remain unclear. In this study, we demonstrated that Nrf2 was significantly elevated in HCC cells and tissues and was correlated with poor prognosis of HCCs. Consistently, Nrf2 significantly promoted HCC cell growth both in vitro and in vivo...
August 30, 2016: Oncotarget
Zhuo Chen, Suixin Liu, Ying Cai, Kangling Xie, Wenliang Zhang, Lei Dong, Yuan Liu, Fan Zheng, Yaoshan Dun, Ning Li
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear...
September 2016: Experimental and Therapeutic Medicine
Kim Hoenderdos, Katharine M Lodge, Robert A Hirst, Cheng Chen, Stefano G C Palazzo, Annette Emerenciana, Charlotte Summers, Adri Angyal, Linsey Porter, Jatinder K Juss, Christopher O'Callaghan, Edwin R Chilvers, Alison M Condliffe
BACKGROUND: The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. METHODS AND RESULTS: Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents...
November 2016: Thorax
Noboru Yamamoto, Yutaka Fujiwara, Kenji Tamura, Shunsuke Kondo, Satoru Iwasa, Yuko Tanabe, Atsushi Horiike, Noriko Yanagitani, Satoru Kitazono, Michiyasu Inatani, Jun Tanaka, Makoto Nishio
Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase inhibitor. This phase Ia/Ib study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of pictilisib in monotherapy or in combination with carboplatin-paclitaxel and bevacizumab (CP + BEV) in Japanese patients with advanced solid tumors or non-squamous non-small cell lung cancer. A standard 3 + 3 dose escalation design was applied. In stage 1, 140, 260, or 340 mg/day of pictilisib was administered once daily to 12 patients with advanced solid tumors...
August 27, 2016: Investigational New Drugs
Yizhu Chen, Wenlong Yang, Lingyu Guo, Xiaolin Wu, Tiantian Zhang, Junling Liu, Junfeng Zhang
Platelets play a crucial role in the development and progression of atherosclerosis-thrombosis and, therefore, antiplatelet drugs are widely used in the treatment of coronary artery disease. Moreover, advances in understanding the biological functions of natural plant products can provide new pharmacological strategies aimed at promoting cardiovascular health. Atractylenolide I (ATL-1), ATL-2, and ATL-3 are the major bioactive components of a Qi tonifying medicinal herb Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala), which is commonly used in traditional Chinese medicine (TCM)...
August 25, 2016: Platelets
Jandee Lee, Woo Kyung Lee, Mi-Youn Seol, Seul Gi Lee, Daham Kim, Hyunji Kim, Jongsun Park, Sang Geun Jung, Woong Youn Chung, Eun Jig Lee, Young Suk Jo
Persistent cellular proliferation and metabolic reprogramming are essential processes in carcinogenesis. Here, we performed Gene Set Enrichment Analysis (GSEA) and found that that LETM1, a mitochondrial calcium transporter, is associated with cellular growth signals such as platelet-derived growth factor (PDGF) receptor signaling and insulin signaling pathways. These results were then verified by qRT-PCR and immnunoblotting. Mechanistically, up-regulation of LETM1 induced YAP1 nuclear accumulation, increasing the expression of PDGFB, PDGFRB and THBS4...
August 20, 2016: Oncotarget
Bin Li, Guangsen Zhang, Cui Li, Ruijuan Li, Jingchen Lu, Zhengxi He, Quan Wang, Zhenzi Peng, Jun Wang, Yeping Dong, Chunfang Zhang, Jie Qiong Tan, Nacef Bahri, Yuexiang Wang, Chaojun Duan
The Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) oncogene can cause chronic eosinophilic leukemia (CEL), but requires IL-5 cytokine participation. In this study, we investigate the mechanism of F/P in collaboration with IL-5 in CEL. The results showed that Lyn, a key effector in the IL-5-motivated eosinophil production, is extensively activated in F/P-positive CEL cells. Lyn can associate and phosphorylate IL-5 receptor α (IL-5RA) in F/P-positive cells. Moreover, the activation of Lyn and IL-5R kinase were strengthened when the cells were stimulated by IL-5...
August 19, 2016: Oncotarget
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