scholarly journals Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Cecilia Vasti ◽  
Henning Witt ◽  
Matilde Said ◽  
Patricia Sorroche ◽  
Hernán García-Rivello ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Ventricular Remodeling ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Neuregulin 1 ◽  
Hypertrophic Response ◽  
Ubiquitin Proteasome

The accumulating evidence demonstrates the essential role of neuregulin-1 signaling in the adult heart, and, moreover, indicates that an impaired neuregulin signaling exacerbates the doxorubicin-mediated cardiac toxicity. Despite this strong data, the specific cardiomyocyte targets of the active erbB2/erbB4 heterodimer remain unknown. In this paper, we examined pathways involved in cardiomyocyte damage as a result of the cardiac sensitization to anthracycline toxicity in the ventricular muscle-specific erbB4 knockout mouse. We performed morphological analyses to evaluate the ventricular remodeling and employed a cDNA microarray to assess the characteristic gene expression profile, verified data by real-time RT-PCR, and then grouped into functional categories and pathways. We confirm the upregulation of genes related to the classical signature of a hypertrophic response, implicating an erbB2-dependent mechanism in doxorubicin-treated erbB4-KO hearts. Our results indicate the remarkable downregulation of IGF-I/PI-3′ kinase pathway and extends our current knowledge by uncovering an altered ubiquitin-proteasome system leading to cardiomyocyte autophagic vacuolization.

scholarly journals The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

2014 ◽  
Vol 19 (4) ◽  
Author(s):  
Patricia Sanz-Ramos ◽  
Javier Dotor ◽  
Iñigo Izal-Azcárate
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Peptide Inhibitors ◽  
Mechanical Environment ◽  
Chondrocyte Phenotype ◽  
Cartilage Cells ◽  
Alk 5

AbstractWe aim to demonstrate the role of Alk receptors in the response of hydrogel expansion. Chondrocytes from rat knees were cultured onto plastic and hydrogel surfaces. Alk-1 and Alk-5 were overexpressed or silenced and the effects on cells during expansion were tested and confirmed using peptide inhibitors for TGFβ. Overexpression of Alk-5 and silencing of Alk-1 led to a loss of the chondrocyte phenotype, proving that they are key regulators of chondrocyte mechanosensing. An analysis of the gene expression profile during the expansion of these modified cartilage cells in plastic showed a better maintenance of the chondrocyte phenotype, at least during the first passages. These passages were also assayed in a mouse model of intramuscular chondrogenesis. Our findings indicate that these two receptors are important mediators in the response of chondrocytes to changes in the mechanical environment, making them suitable targets for modulating chondrogenesis. Inhibition of TGFβ could also be effective in improving chondrocyte activity in aged or expanded cells that overexpress Alk-1.

Cell death gene expression profile: Role of RIPK2 in dengue virus-mediated apoptosis

2011 ◽  
Vol 156 (1-2) ◽  
pp. 25-34 ◽  
Author(s):  
Atthapan Morchang ◽  
Umpa Yasamut ◽  
Janjuree Netsawang ◽  
Sansanee Noisakran ◽  
Wiyada Wongwiwat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Dengue Virus ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Cell Death Gene

scholarly journals Inhibition of the Ubiquitin-Proteasome System Prevents Vaccinia Virus DNA Replication and Expression of Intermediate and Late Genes

2009 ◽  
Vol 83 (6) ◽  
pp. 2469-2479 ◽  
Author(s):  
P. S. Satheshkumar ◽  
Luis C. Anton ◽  
Patrick Sanz ◽  
Bernard Moss
Keyword(s):  
Gene Expression ◽  
Vaccinia Virus ◽  
Proteasome Inhibitors ◽  
Ubiquitin Proteasome System ◽  
Late Gene ◽  
Late Gene Expression ◽  
Viral Dna ◽  
Late Genes ◽  
Ubiquitin Proteasome

ABSTRACT The ubiquitin-proteasome system has a central role in the degradation of intracellular proteins and regulates a variety of functions. Viruses belonging to several different families utilize or modulate the system for their advantage. Here we showed that the proteasome inhibitors MG132 and epoxomicin blocked a postentry step in vaccinia virus (VACV) replication. When proteasome inhibitors were added after virus attachment, early gene expression was prolonged and the expression of intermediate and late genes was almost undetectable. By varying the time of the removal and addition of MG132, the adverse effect of the proteasome inhibitors was narrowly focused on events occurring 2 to 4 h after infection, the time of the onset of viral DNA synthesis. Further analyses confirmed that genome replication was inhibited by both MG132 and epoxomicin, which would account for the effect on intermediate and late gene expression. The virus-induced replication of a transfected plasmid was also inhibited, indicating that the block was not at the step of viral DNA uncoating. UBEI-41, an inhibitor of the ubiquitin-activating enzyme E1, also prevented late gene expression, supporting the role of the ubiquitin-proteasome system in VACV replication. Neither the overexpression of ubiquitin nor the addition of an autophagy inhibitor was able to counter the inhibitory effects of MG132. Further studies of the role of the ubiquitin-proteasome system for VACV replication may provide new insights into virus-host interactions and suggest potential antipoxviral drugs.

scholarly journals PB2193 GENE EXPRESSION PROFILE IN PRIMARY MYELOFIBROSIS: ROLE OF ASXL1

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 983-984
Author(s):  
S. Sánchez Sosa ◽  
C. Bilbao Sieyro ◽  
Y. Florido Ortega ◽  
E. González Pérez ◽  
M. D. L. N. Saez Perdomo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Primary Myelofibrosis
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