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Beta cells AND GSK

Wenji He, Xinyu Yan, Sanqiang Pan
Amphetamine (AMPH) abuse can influence neuropsychiatric disorders and cell apoptosis by interfering with the protein kinase B/ glycogen synthase kinase 3 beta (AKT/GSK3β) pathway. However, the mechanisms underlying this regulation are poorly understood. Using PC12 cells, we found that AMPH inhibited AKT and GSK-3β phosphorylation levels and increased total GSK-3β levels. Furthermore, AMPH caused an increase in the activity of protein phosphatase 2 (PP2A), a signaling protein upstream of AKT, which in turn inhibited phosphorylated AKT levels...
March 6, 2018: Neurotoxicity Research
Fernanda Barbisan, Verônica Farina Azzolin, Gustavo Cardenas Monteiro, Cibele F Teixeira, Moisés Henrique Mastella, Vitor Bueno, Marta Maria Medeiros Frescura Duarte, Glauber Wagner, Pedro Antônio Schmidt do Prado-Lima, Euler Esteves Ribeiro, Ivana B M da Cruz
INTRODUCTION: Lithium (Li), a mood stabilizer used to treat bipolar disorder (BP) symptoms has important anti-inflammatory effects by downregulation of glycogen synthase kinase-3 beta (GSK-3β). However, sometime Li effect is not efficient in some patients suggesting genetic interference. Previous investigations described association between a genetic superoxide‑hydrogen (S-HP) imbalance caused by a superoxide dismutase manganese dependent gene polymorphism (Val16Ala-SOD2 SNP, rs4880) and differential anti-inflammatory response of some drugs and bioactive molecules...
February 18, 2018: Gene
Shohreh Majd, Zohreh Majd, Simon Koblar, John Power
Hyperphosphorylation of tau is one of the main hallmarks for Alzheimer's disease (AD) and many other tauopathies. Norepinephrine (NE), a stress-related hormone 17-β-estradiol (E2) and thought to influence tau phosphorylation (p-tau) and AD pathology. The controversy around the impact of NE and E2 requires further clarification. Moreover, the combination effect of physiological and psychological stress and estrogen alteration during menopause, which affect p-tau, has not been addressed. Exposure to E2 is believed to reduce NE release, however, the link between these two hormones and AD at cellular level was also remained unknown...
February 7, 2018: Molecular and Cellular Neurosciences
Yuan Wang, Shaowei Yin, Hang Xue, Yating Yang, Nan Zhang, Ping Zhao
Advancements in fetal intervention procedures have led to increases in the number of pregnant women undergoing general anesthesia during the second trimester-a period characterized by extensive proliferation of fetal neural stem cells (NSCs). However, few studies have investigated the effects of mid-gestational sevoflurane exposure on fetal NSC proliferation or postnatal learning and memory function. In the present study, pregnant rats were randomly assigned to a control group (C group), a low sevoflurane concentration group (2%; L group), a high sevoflurane concentration group (3...
January 31, 2018: Developmental Biology
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
Bo-Bo Zhao, Hui-Jie Guo, Yang Liu, Xing-Yan Luo, Shu-Xia Yang, Yan-Tang Wang, Xiao Leng, Chun-Fen Mo, Qiang Zou
Benzoxazole and its derivatives have been widely studied in recent years due to their various biological properties. A previous study has demonstrated that K313 (1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)), a novel benzoxazole derivative, inhibits T cell proliferation to yield immunosuppressive effects. However, there are no related reports about its anti-inflammatory effects. In the present study, we investigated the anti-inflammatory properties and the underlying molecular mechanism of K313 in lipopolysaccharide (LPS)-induced RAW264...
January 18, 2018: Journal of Cellular Biochemistry
Yuekun Zhu, Qingxin Zhou, Guiling Zhu, Yanwei Xing, Shiqiang Li, Niansheng Ren, Tianyou Liu, Anlong Zhu, Yuxian Bai, Daxun Piao
Zinc finger protein 281 (ZNF281) has been recently shown to be critical for CRC progression. However, the immediate upstream regulators of ZNF281 remain unclear. Here we reported that the E3 ligase the β-transducin repeat-containing protein 2 (β-TrCP2) governs the ubiquitination and degradation of ZNF281. In human CRC specimens, endogenous β-TrCP2 were inversely correlated with ZNF281. Beta-TrCP2 reversed the phenotype of CRC cell with overexpressed ZNF281. Moreover, we found that glycogen synthase kinase 3β (GSK-3β), not GSK-α, could bind to and phosphorylate ZNF281 at one consensus motif (TSGEHS; phosphorylation site is shown in italics), which promotes the interaction of ZNF281 with β-TrCP2, not β-TrCP1, and leads to the subsequent ubiquitination and degradation of phosphorylated ZNF281...
October 24, 2017: Oncotarget
Denan Zhang, Lei Liu, Lin Pang, Qing Jin, Kehui Ke, Ming Hu, Jingbo Yang, Weifang Ma, Hongbo Xie, Xiujie Chen
Glycogen synthase kinase-3 beta (GSK-3β) is involved in multiple signaling pathways. Consistent with its critical roles in normal cells, abnormalities in GSK-3β activity have been implicated in diabetes, heart disease, Parkinson disease and Alzheimer's disease. In this study, a series of new scaffolds of small molecule inhibitors of GSK-3β were identified by virtual screening and bioassay. Candidates that adhere to drug-like criteria from a virtual library of compounds were tested using computational docking studies...
November 16, 2017: Journal of Cellular Biochemistry
Debmita Chatterjee, Apurba Bandyopadhyay, Nilendu Sarma, Santanu Basu, Tarit Roychowdhury, Sib Sankar Roy, Ashok K Giri
Arsenic induced senescence (AIS) has been identified in the population of West Bengal, India very recently. Also there is a high incidence of arsenic induced peripheral neuropathy (PN) throughout India. However, the epigenetic regulation of AIS and its contribution in arsenic induced PN remains unexplored. We recruited seventy two arsenic exposed and forty unexposed individuals from West Bengal to evaluate the role of senescence associated miRNAs (SA-miRs) in AIS and their involvement if any, in PN. The downstream molecules of the miRNA associated with the disease outcome, was also checked by immuoblotting...
November 3, 2017: Environmental Pollution
Guang-Zhe Li, Fang Liu, Cui Xu, Jing-Yang Li, Yan-Ji Xu
Amyloid beta (Aβ) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. The present study was conducted to investigate whether the combined treatment with selenium (Se) and zinc (Zn) offers more beneficial effects than that provided by either of them alone in reversing Aβ25-35-induced neurotoxicity in PC12 cells. Cells were pretreated with 0.1 μmol/L of Se and Zn for 4 h, after treated with 10 mmol/L Aβ25-35 for 24 h. Cells were divided into control and five treated groups, and received either 10 mmol/L Aβ25-35,10 mmol/L Aβ25-35 + 0...
October 28, 2017: Biological Trace Element Research
Zhaoxiang Ren, Pengju Yan, Liushuai Zhu, Huicui Yang, Yafei Zhao, Brian P Kirby, John L Waddington, Xuechu Zhen
RATIONALE: Major depressive disorder (MDD) is a highly prevalent illness that affects large populations across the world, and increasing evidence suggests that neuroinflammation and levels of brain-derived neurotrophic factor (BDNF) are closely related to depression. Dihydromyricetin (DHM) is a kind of flavonoid natural product that has been reported to display multiple pharmacological effects, including anti-inflammatory and anti-oxidative properties, and these may contribute to ameliorate MDD...
October 20, 2017: Psychopharmacology
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Alzheimer's disease (AD) is a neurodegenerative disease, in which the primary etiology remains unknown. AD presents amyloid beta (Aβ) protein aggregation and neurofibrillary plaque deposits. AD shows oxidative stress and chronic inflammation. In AD, canonical Wingless-Int (Wnt)/β-catenin pathway is downregulated, whereas peroxisome proliferator-activated receptor γ (PPARγ) is increased. Downregulation of Wnt/β-catenin, through activation of glycogen synthase kinase-3β (GSK-3β) by Aβ, and inactivation of phosphatidylinositol 3-kinase/Akt signaling involve oxidative stress in AD...
October 1, 2017: Acta Biochimica et Biophysica Sinica
X Gao, X Li, C Qian, F Li, Y Zhang, L Dang, X Xiao, F Liu, H Li, X Zhang
MicroRNA involves in regulating behavior of neural stem/precursor cells (NSPCs), thus it offers the potential to treat central nervous system disease. However, the effect of miR-21 on NSPCs remains unknown. In this study, we demonstrated that miR-21 reduced proliferation and promoted neural differentiation in NSPCs via regulating the activation of AKT and GSK-3β signaling pathways in vitro. During differentiation of NSPCs, the expression of miR-21 was increased in a time-dependent manner by qRT-PCR. Synthesized pre-miR-21 or anti-miR-21 was transfected into NSPCs, thereby efficiently overexpressing or knocking down miR-21...
October 31, 2016: Cellular and Molecular Biology
Yuan-Yuan Jiang, Juan Wen, Cheng Gong, Shuang Lin, Ca Ixia Zhang, Sheng Chen, Wei Cheng, Huang Li
Osteoarthritis induced by compressive mechanical force is characterized by decreased chondrocyte proliferation and degradation of the ECM. To examine underlying mechanisms of the pathological changes of mandibular cartilage induced by compressive mechanical force, an established animal model was used to examine Wnt signaling activation by glycogen synthase kinase-3 beta (GSK3β) inhibitor 6-Bromoindirubin-3'-oxime (BIO) injection in vivo. Histological changes in mandibular cartilage were assessed via hematoxylin & eosin (HE), masson, and alcian blue staining...
September 28, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Rengasamy Balakrishnan, Namasivayam Elangovan, Thangavel Mohankumar, Jegadeesan Nataraj, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Mohamed Musthafa Essa, Mohammed Akbar, Mohammed Abdul Sattar Khan
The present study was carried out to investigate the neuroprotective effects of isolongifolene (ILF), a tricyclic sesquiterpene of Murraya koenigii, against rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis in a cellular model. SH-SY5Y human neuroblastoma cells were divided into four experimental groups (control, rotenone (100 nM), ILF (10 microM) + rotenone (100 nanoM), ILF 10 microM alone treated) based on 3-(4, 5-dimethyl 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results of the present study showed that the ILF treatment significantly alleviated rotenone-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in SH-SY5Y cells...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
Yuchen Wang, Maureen R Newman, Marian Ackun-Farmmer, Michael P Baranello, Tzong-Jen Sheu, J Edward Puzas, Danielle S W Benoit
Despite several decades of progress, bone-specific drug delivery is still a major challenge. Current bone-acting drugs require high-dose systemic administration which decreases therapeutic efficacy and increases off-target tissue effects. Here, a bone-targeted nanoparticle (NP) delivery system for a β-catenin agonist, 3-amino-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-N-(pyridin-3-yl)pyrazine-2-carboxamide, a glycogen synthase kinase 3 beta (GSK-3β) inhibitor, was developed to enhance fracture healing...
September 26, 2017: ACS Nano
Cinzia Giagulli, Pasqualina D'Ursi, Wangxiao He, Simone Zorzan, Francesca Caccuri, Kristen Varney, Alessandro Orro, Stefania Marsico, Benoît Otjacques, Carlo Laudanna, Luciano Milanesi, Riccardo Dolcetti, Simona Fiorentini, Wuyuan Lu, Arnaldo Caruso
Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha)...
July 26, 2017: Scientific Reports
Simone Brogi, Anna Ramunno, Lida Savi, Giulia Chemi, Gloria Alfano, Alessandra Pecorelli, Erika Pambianchi, Paola Galatello, Giulia Compagnoni, Federico Focher, Giuseppe Biamonti, Giuseppe Valacchi, Stefania Butini, Sandra Gemma, Giuseppe Campiani, Margherita Brindisi
The manuscript deals with the design, synthesis and biological evaluation of novel benzoxazinone-based and indole-based compounds as multifunctional neuroprotective agents. These compounds inhibit human adenosine kinase (hAK) and human glycogen synthase kinase 3 beta (hGSK-3β) enzymes. Computational analysis based on a molecular docking approach underlined the potential structural requirements for simultaneously targeting both proteins' allosteric sites. In silico hints drove the synthesis of appropriately decorated benzoxazinones and indoles (5a-s, and 6a-c) and biochemical analysis revealed their behavior as allosteric inhibitors of hGSK-3β...
September 29, 2017: European Journal of Medicinal Chemistry
Junying Liu, Guangdong Zhang, Yanping Lv, Xiaoyang Zhang, Cui Ying, Suocheng Yang, Xin Kong, Yanzhang Yu
The phosphoinositide 3-kinase pathway is one of the most commonly altered pathways in human cancers. The serum/glucocorticoid-regulated kinase (SGK) family of serine/threonine kinases consists of three isoforms, SGK1, SGK2, and SGK3. This family of kinases is highly homologous to the AKT kinase family, sharing similar upstream activators and downstream targets. Few studies have investigated the role of SGK2 in hepatocellular carcinoma. Here, we report that SGK2 expression levels were upregulated in hepatocellular carcinoma tissues and human hepatoma cell lines compared to the adjacent normal liver tissues and a normal hepatocyte line, respectively...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sarika Chaudhari, Weizu Li, Yanxia Wang, Hui Jiang, Yuhong Ma, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca(2+) entry (SOCE) in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor-β1 (TGF-β1)/Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGF-β1 (5 ng/ml for 15 h) significantly increased Smad3 phosphorylation, as evaluated by immunoblot...
September 1, 2017: American Journal of Physiology. Renal Physiology
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