Neurotrophins Require Distinct Extracellular Signals to Promote the Survival of CNS Neurons in Vitro

2000 ◽  
Vol 165 (1) ◽  
pp. 125-135 ◽  
Author(s):  
Barbara Franke ◽  
Nadhim Bayatti ◽  
Jürgen Engele
Keyword(s):  
Extracellular Signals ◽  
Cns Neurons

scholarly journals Development of Novel Zn2+ Loaded Nanoparticles Designed for Cell-Type Targeted Drug Release in CNS Neurons: In Vitro Evidences

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e17851 ◽  
Author(s):  
Andreas M. Grabrucker ◽  
Craig C. Garner ◽  
Tobias M. Boeckers ◽  
Lucia Bondioli ◽  
Barbara Ruozi ◽  
...  
Keyword(s):  
Drug Release ◽  
Cell Type ◽  
Cns Neurons ◽  
Targeted Drug

scholarly journals Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors

1999 ◽  
Vol 19 (6) ◽  
pp. 4028-4038 ◽  
Author(s):  
Shen-Hsi Yang ◽  
Alex Galanis ◽  
Andrew D. Sharrocks
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Map Kinases ◽  
Biological Response ◽  
Extracellular Signals ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an important event in the conversion of extracellular signals into a cellular response. However, the existence of multiple MAP kinases which phosphorylate similar phosphoacceptor motifs poses a problem in maintaining substrate specificity and hence the correct biological response. Both the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) subfamilies of MAP kinases use a second specificity determinant and require docking to their transcription factor substrates to achieve maximal substrate activation. In this study, we demonstrate that among the different MAP kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38α and p38β2. The efficiency of phosphorylation in vitro and transcriptional activation in vivo of MEF2A and MEF2C by these p38 subtypes requires the presence of a kinase docking domain (D-domain). Furthermore, the D-domain from MEF2A is sufficient to confer p38 responsiveness on different transcription factors, and reciprocal effects are observed upon the introduction of alternative D-domains into MEF2A. These results therefore contribute to our understanding of signalling to MEF2 transcription factors and demonstrate that the requirement for substrate binding by MAP kinases is an important facet of three different subclasses of MAP kinases (ERK, JNK, and p38).

Death of cultured postnatal rat CNS neurons by in vitro hypoxia with special reference to toxicity

1994 ◽  
Vol 19 (3) ◽  
pp. 279-285 ◽  
Author(s):  
Yukio Akaneya ◽  
Mitsuo Takahashi ◽  
Hiroshi Hatanaka
Keyword(s):  
Special Reference ◽  
Cns Neurons ◽  
Rat Cns

Intracellular matrix metalloproteinase-2 (MMP-2) regulates human platelet activation via hydrolysis of talin

2014 ◽  
Vol 111 (01) ◽  
pp. 140-153 ◽  
Author(s):  
Christopher Mason ◽  
Stephen Lynch ◽  
James Benjamin ◽  
Dani Ashak ◽  
Jamunabai M. Prakash ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Matrix Metalloproteinase ◽  
Platelet Activation ◽  
Matrix Metalloproteinase 2 ◽  
Activation Pathway ◽  
Extracellular Signals ◽  
Mmp Inhibitor ◽  
Activation Mechanisms ◽  
Vitro Analysis

SummaryMatrix metalloproteinase (MMP) activity is generally associated with normal or pathological extracellular processes such as tissue remodeling in growth and development or in tumor metastasis and angiogenesis. Platelets contain at least three MMPs, 1, 2 and 9 that have been reported to stimulate or inhibit agonist-induced platelet aggregation via extracellular signals. The non-selective Zn+2 chelating MMP inhibitor, 1,10-phenanthroline, and the serine protease inhibitor, AEBSF, were found to inhibit all tested agonist-induced platelet aggregation reactions. In vitro analysis demonstrated that 1,10-phenanthroline completely inhibited MMP-1,2,and 9 but had little to no effect on calpain activity while the converse was true with AEBSF. We now demonstrate that MMP-2 functions intracellularly to regulate agonistinduced platelet aggregations via the hydrolytic activation of talin, the presumed final activating factor of glycoprotein (GP)IIb/IIIa integrin (the inside-out signal). Once activated GPIIb/IIIa binds the dimeric fibrinogen molecule required for platelet aggregation. The active intracellular MMP-2 molecule is complexed with JAK 2/STAT 3, as demonstrated by the fact that all three proteins are co-immunoprecipitated with either anti-JAK 2, or anti-STAT 3 antibodies and by immunofluorescence studies. The MMP-2 platelet activation pathway can be synergistically inhibited with the non-selective MMP inhibitor, 1,10-phenanthroline, plus a JAK 2 inhibitor. This activation pathway is distinct from the previously reported calpain-talin activating pathway. The identification of a new central pathway for platelet aggregation presents new potential targets for drug regulation and furthers our understanding of the complexity of platelet activation mechanisms.

scholarly journals Roles of hnRNP A1, SR Proteins, and p68 Helicase in c-H-ras Alternative Splicing Regulation

2003 ◽  
Vol 23 (8) ◽  
pp. 2927-2941 ◽  
Author(s):  
Sònia Guil ◽  
Renata Gattoni ◽  
Montserrat Carrascal ◽  
Joaquín Abián ◽  
James Stévenin ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Sr Proteins ◽  
Splicing Regulation ◽  
Hnrnp A1 ◽  
Carboxy Terminus ◽  
Extracellular Signals ◽  
Nuclear Extracts ◽  
Acting In Concert

ABSTRACT Human ras genes play central roles in coupling extracellular signals with complex intracellular networks controlling proliferation, differentiation, and apoptosis, among others processes. c-H-ras pre-mRNA can be alternatively processed into two mRNAs due to the inclusion or exclusion of the alternative exon IDX; this renders two proteins, p21H-Ras and p19H-RasIDX, which differ only at the carboxy terminus. Here, we have characterized some of the cis-acting sequences and trans-acting factors regulating IDX splicing. A downstream intronic silencer sequence (rasISS1), acting in concert with IDX, negatively regulates upstream intron splicing. This effect is mediated, at least in part, by the binding of hnRNP A1. Depletion and add-back experiments in nuclear extracts have confirmed hnRNP A1's inhibitory role in IDX splicing. Moreover, the addition of two SR proteins, SC35 and SRp40, can counteract this inhibition by strongly promoting the splicing of the upstream intron both in vivo and in vitro. Further, the RNA-dependent helicase p68 is also associated with both IDX and rasISS1 RNA, and suppression of p68 expression in HeLa cells by RNAi experiments results in a marked increase of IDX inclusion in the endogenous mRNA, suggesting a role for this protein in alternative splicing regulation.

scholarly journals Different species of phosphatidic acid are produced during neuronal growth and neurosecretion

OCL ◽  
2018 ◽  
Vol 25 (4) ◽  
pp. D408 ◽  
Author(s):  
Emeline Tanguy ◽  
Qili Wang ◽  
Pierre Coste de Bagneaux ◽  
Laetitia Fouillen ◽  
Tamou Thahouly ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Neuronal Development ◽  
Neuronal Degeneration ◽  
Good Health ◽  
Cellular Functions ◽  
Extracellular Signals ◽  
Molecular Nature

Although originally restricted to their structural role as major constituents of membranes, lipids are now well-defined actors to integrate intracellular or extracellular signals. Accordingly, it has been known for decades that lipids, especially those coming from diet, are important to maintain normal physiological functions and good health. This is especially the case to maintain proper cognitive functions and avoid neuronal degeneration. But besides this empiric knowledge, the exact molecular nature of lipids in cellular signaling, as well as their precise mode of action are only starting to emerge. The recent development of novel pharmacological, molecular, cellular and genetic tools to study lipids in vitro and in vivo has contributed to this improvement in our knowledge. Among these important lipids, phosphatidic acid (PA) plays a unique and central role in a great variety of cellular functions. This article will review the different findings illustrating the involvement of PA generated by phospholipase D (PLD) and diacylglycerol kinases (DGK) in the different steps of neuronal development and neurosecretion. We will also present lipidomic evidences indicating that different species of PA are synthesized during these two key neuronal phenomena.

scholarly journals cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1433
Author(s):  
Mohamed Elnagdy ◽  
Shirish Barve ◽  
Craig McClain ◽  
Leila Gobejishvili
Keyword(s):  
Liver Disease ◽  
Therapeutic Potential ◽  
Hepatocellular Cancer ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Signaling ◽  
In Vivo Models ◽  
Extracellular Signals

The importance of cyclic adenosine monophosphate (cAMP) in cellular responses to extracellular signals is well established. Many years after discovery, our understanding of the intricacy of cAMP signaling has improved dramatically. Multiple layers of regulation exist to ensure the specificity of cellular cAMP signaling. Hence, disturbances in cAMP homeostasis could arise at multiple levels, from changes in G protein coupled receptors and production of cAMP to the rate of degradation by phosphodiesterases. cAMP signaling plays critical roles in metabolism, inflammation and development of fibrosis in several tissues. Alcohol-associated liver disease (ALD) is a multifactorial condition ranging from a simple steatosis to steatohepatitis and fibrosis and ultimately cirrhosis, which might lead to hepatocellular cancer. To date, there is no FDA-approved therapy for ALD. Hence, identifying the targets for the treatment of ALD is an important undertaking. Several human studies have reported the changes in cAMP homeostasis in relation to alcohol use disorders. cAMP signaling has also been extensively studied in in vitro and in vivo models of ALD. This review focuses on the role of cAMP in the pathobiology of ALD with emphasis on the therapeutic potential of targeting cAMP signaling for the treatment of various stages of ALD.

scholarly journals Regulation of the G1/S Transition in Hepatocytes: Involvement of the Cyclin-Dependent Kinase Cdk1 in the DNA Replication

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Anne Corlu ◽  
Pascal Loyer
Keyword(s):  
Dna Replication ◽  
Liver Regeneration ◽  
Primary Cultures ◽  
G1 Phase ◽  
Cyclin Dependent Kinase ◽  
Restriction Point ◽  
Extracellular Signals ◽  
Combined Use

A singular feature of adult differentiated hepatocytes is their capacity to proliferate allowing liver regeneration. This review emphasizes the literature published over the last 20 years that established the most important pathways regulating the hepatocyte cell cycle. Our article also aimed at illustrating that many discoveries in this field benefited from the combined use ofin vivomodels of liver regeneration andin vitromodels of primary cultures of human and rodent hepatocytes. Using these models, our laboratory has contributed to decipher the different steps of the progression into the G1 phase and the commitment to S phase of proliferating hepatocytes. We identified the mitogen dependent restriction point located at the two-thirds of the G1 phase and the concomitant expression and activation of both Cdk1 and Cdk2 at the G1/S transition. Furthermore, we demonstrated that these two Cdks contribute to the DNA replication. Finally, we provided strong evidences that Cdk1 expression and activation is correlated to extracellular matrix degradation upon stimulation by the pro-inflammatory cytokine TNFαleading to the identification of a new signaling pathway regulating Cdk1 expression at the G1/S transition. It also further confirms the well-orchestrated regulation of liver regeneration via multiple extracellular signals and pathways.

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