scholarly journals Transcriptional Profiling Reveals Ribosome Biogenesis, Microtubule Dynamics and Expression of Specific lncRNAs to be Part of a Common Response to Cell-Penetrating Peptides

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1567
Author(s):  
Tomas Venit ◽  
Moataz Dowaidar ◽  
Maxime Gestin ◽  
Syed Raza Mahmood ◽  
Ülo Langel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Bilayers ◽  
Hela Cells ◽  
Ribosome Biogenesis ◽  
Time Course ◽  
Transcriptional Profiling ◽  
Cell Penetrating Peptides ◽  
Microtubule Dynamics ◽  
Cell Penetrating ◽  
Common Response

Cell-penetrating peptides (CPPs) are short peptides that are able to efficiently penetrate cellular lipid bilayers. Although CPPs have been used as carriers in conjugation with certain cargos to target specific genes and pathways, how rationally designed CPPs per se affect global gene expression has not been investigated. Therefore, following time course treatments with 4 CPPs-penetratin, PepFect14, mtCPP1 and TP10, HeLa cells were transcriptionally profiled by RNA sequencing. Results from these analyses showed a time-dependent response to different CPPs, with specific sets of genes related to ribosome biogenesis, microtubule dynamics and long-noncoding RNAs being differentially expressed compared to untreated controls. By using an image-based high content phenotypic profiling platform we confirmed that differential gene expression in CPP-treated HeLa cells strongly correlates with changes in cellular phenotypes such as increased nucleolar size and dispersed microtubules, compatible with altered ribosome biogenesis and cell growth. Altogether these results suggest that cells respond to different cell penetrating peptides by alteration of specific sets of genes, which are possibly part of the common response to such stimulus.

Applications of cell-penetrating peptides in regulation of gene expression

2007 ◽  
Vol 35 (4) ◽  
pp. 770-774 ◽  
Author(s):  
P. Järver ◽  
K. Langel ◽  
S. El-Andaloussi ◽  
Ü. Langel
Keyword(s):  
Gene Expression ◽  
Lipid Bilayers ◽  
Regulation Of Gene Expression ◽  
Cell Penetrating Peptides ◽  
Remarkable Feature ◽  
Cell Penetrating ◽  
Plasmid Delivery ◽  
Interfering Rna

CPPs (cell-penetrating peptides) can be defined as short peptides that are able to efficiently penetrate cellular lipid bilayers. Because of this remarkable feature, they are excellent candidates regarding alterations in gene expression. CPPs have been utilized in in vivo and in vitro experiments as delivery vectors for different bioactive cargoes. This review focuses on the experiments performed in recent years where CPPs have been used as vectors for multiple effectors of gene expression such as oligonucleotides for antisense, siRNA (small interfering RNA) and decoy dsDNA (double-stranded DNA) applications, and as transfection agents for plasmid delivery.

Decoding the Entry of Two Novel Cell-Penetrating Peptides in HeLa Cells:  Lipid Raft-Mediated Endocytosis and Endosomal Escape†

Biochemistry ◽  
2005 ◽  
Vol 44 (1) ◽  
pp. 72-81 ◽  
Author(s):  
Christina Foerg ◽  
Urs Ziegler ◽  
Jimena Fernandez-Carneado ◽  
Ernest Giralt ◽  
Robert Rennert ◽  
...  
Keyword(s):  
Lipid Raft ◽  
Hela Cells ◽  
Cell Penetrating Peptides ◽  
Endosomal Escape ◽  
Cell Penetrating

Transcriptional profiling of in vitro smooth muscle cell differentiation identifies specific patterns of gene and pathway activation

2004 ◽  
Vol 19 (3) ◽  
pp. 292-302 ◽  
Author(s):  
Joshua M. Spin ◽  
Shriram Nallamshetty ◽  
Raymond Tabibiazar ◽  
Euan A. Ashley ◽  
Jennifer Y. King ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Large Scale ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Transcriptional Profiling ◽  
Temporal Trends

Mesodermal and epidermal precursor cells undergo phenotypic changes during differentiation to the smooth muscle cell (SMC) lineage that are relevant to pathophysiological processes in the adult. Molecular mechanisms that underlie lineage determination and terminal differentiation of this cell type have received much attention, but the genetic program that regulates these processes has not been fully defined. Study of SMC differentiation has been facilitated by development of the P19-derived A404 embryonal cell line, which differentiates toward this lineage in the presence of retinoic acid and allows selection for cells adopting a SMC fate through a differentiation-specific drug marker. We sought to define global alterations in gene expression by studying A404 cells during SMC differentiation with oligonucleotide microarray transcriptional profiling. Using an in situ 60-mer array platform with more than 20,000 mouse genes derived from the National Institute on Aging clone set, we identified 2,739 genes that were significantly upregulated after differentiation was completed (false-detection ratio <1). These genes encode numerous markers known to characterize differentiated SMC, as well as many unknown factors. We further characterized the sequential patterns of gene expression during the differentiation time course, particularly for known transcription factor families, providing new insights into the regulation of the differentiation process. Changes in genes associated with specific biological ontology-based pathways were evaluated, and temporal trends were identified for functional pathways. In addition to confirming the utility of the A404 model, our data provide a large-scale perspective of gene regulation during SMC differentiation.

scholarly journals Cell penetrating peptides can exert biological activity: a review

2010 ◽  
Vol 1 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Jamie Brugnano ◽  
Brian C. Ward ◽  
Alyssa Panitch
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Cell Membrane ◽  
Recent Literature ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating ◽  
Different Cell Types ◽  
Traditional Understanding

AbstractCell penetrating peptides (CPPs) have been successful in delivering cargo into many different cell types and are an important alternative to other methods of permeation that might damage the integrity of the cell membrane. The traditional view of CPPs is that they are inert molecules that can be successfully used to deliver many cargos intracellularly. The goal of this review is to challenge this traditional understanding of CPPs. Recent literature has demonstrated that CPPs themselves can convey biological activity, including the alteration of gene expression and inhibition of protein kinases and proteolytic activity. Further characterization of CPPs is required to determine the extent of this activity. Research into the use of CPPs for intracellular delivery should continue with investigators being aware of these recent results.

scholarly journals Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis

2015 ◽  
Vol 119 (4) ◽  
pp. 321-327 ◽  
Author(s):  
Tyler J. Kirby ◽  
Jonah D. Lee ◽  
Jonathan H. England ◽  
Thomas Chaillou ◽  
Karyn A. Esser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Ribosome Biogenesis ◽  
Time Course ◽  
28S Rrna ◽  
Older Individuals ◽  
Hypertrophic Response ◽  
Protein Encoding ◽  
Encoding Genes ◽  
Old Mice

The ability of skeletal muscle to hypertrophy in response to a growth stimulus is known to be compromised in older individuals. We hypothesized that a change in the expression of protein-encoding genes in response to a hypertrophic stimulus contributes to the blunted hypertrophy observed with aging. To test this hypothesis, we determined gene expression by microarray analysis of plantaris muscle from 5- and 25-mo-old mice subjected to 1, 3, 5, 7, 10, and 14 days of synergist ablation to induce hypertrophy. Overall, 1,607 genes were identified as being differentially expressed across the time course between young and old groups; however, the difference in gene expression was modest, with cluster analysis showing a similar pattern of expression between the two groups. Despite ribosome protein gene expression being higher in the aged group, ribosome biogenesis was significantly blunted in the skeletal muscle of aged mice compared with mice young in response to the hypertrophic stimulus (50% vs. 2.5-fold, respectively). The failure to upregulate pre-47S ribosomal RNA (rRNA) expression in muscle undergoing hypertrophy of old mice indicated that rDNA transcription by RNA polymerase I was impaired. Contrary to our hypothesis, the findings of the study suggest that impaired ribosome biogenesis was a primary factor underlying the blunted hypertrophic response observed in skeletal muscle of old mice rather than dramatic differences in the expression of protein-encoding genes. The diminished increase in total RNA, pre-47S rRNA, and 28S rRNA expression in aged muscle suggest that the primary dysfunction in ribosome biogenesis occurs at the level of rRNA transcription and processing.

scholarly journals Ionpair-π interactions favor cell penetration of arginine/tryptophan-rich cell-penetrating peptides

2019 ◽  
Author(s):  
Astrid Walrant ◽  
Antonio Bauzá ◽  
Claudia Girardet ◽  
Isabel D. Alves ◽  
Sophie Lecomte ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Density Functional ◽  
Molecular Mechanisms ◽  
Cell Penetrating Peptides ◽  
Membrane Phospholipids ◽  
Active Peptides ◽  
Π Interactions ◽  
Cell Penetrating ◽  
Membrane Active Peptides

AbstractCell-penetrating peptides (CPPs) internalization can occur both by endocytosis and direct translocation through the cell membrane. These different entry routes suggest that molecular partners at the plasma membrane, phospholipids or glycosaminoglycans (GAGs), bind CPPs with different affinity or selectivity. The analysis of sequence-dependent interactions of CPPs with lipids and GAGs should lead to a better understanding of the molecular mechanisms underlying their internalization. CPPs are short sequences generally containing a high number of basic arginines and lysines and sometimes aromatic residues, in particular tryptophans. Tryptophans are crucial residues in membrane-active peptides, because they are important for membrane interaction. Membrane-active peptides often present facial amphiphilicity, which also promote the interaction with lipid bilayers. To study the role of Trp and facial amphiphilicity in cell interaction and penetration of CPPs, a nonapeptide series containing only Arg, Trp or D-Trp residues at different positions was designed. Our quantitative study indicates that to maintain/increase the uptake efficiency, Arg can be advantageously replaced by Trp in the nonapeptides. The presence of Trp in oligoarginines increases the uptake in cells expressing GAGs at their surface, when it only compensates for the loss of Arg and maintains similar peptide uptake in GAG-deficient cells. In addition, we show that facial amphiphilicity is not required for efficient uptake of these nonapeptides. Thermodynamic analyses point towards a key role of Trp that highly contributes to the binding enthalpy of complexes formation. Density functional theory (DFT) analysis highlights that salt bridge-π interactions play a crucial role for the GAG-dependent entry mechanisms.

scholarly journals Signaling Pathway of Histamine H1 Receptor-Mediated Histamine H1 Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells

2021 ◽  
Vol 43 (3) ◽  
pp. 1243-1254
Author(s):  
Hiroyuki Mizuguchi ◽  
Yuko Miyamoto ◽  
Takuma Terao ◽  
Haruka Yoshida ◽  
Wakana Kuroda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Hela Cells ◽  
Time Course ◽  
Receptor Gene ◽  
Selective Inhibitor ◽  
H1 Receptor ◽  
Promoter Assay ◽  
Peripheral Tissues ◽  
Histamine H1 Receptor

Histamine H1 receptor (H1R) is one of the targets of histamine in the nervous system and the peripheral tissues. Protein kinase Cδ (PKCδ) signaling is involved in histamine-induced upregulation of H1R gene expression in HeLa cells. Histamine also upregulates H1R gene expression in U-373 MG cells. However, the molecular signaling of this upregulation is still unclear. Here, we investigated the molecular mechanism of histamine-induced H1R gene upregulation in U-373 MG cells. Histamine-induced H1R gene upregulation was inhibited by H1R antagonist d-chlorpheniramine, but not by ranitidine, ciproxifan, or JNJ77777120, and H2R, H3R, or H4R antagonists, respectively. Ro-31-8220 and Go6976 also suppressed this upregulation, however, the PKCδ selective inhibitor rottlerin and the PKCβ selective inhibitor Ly333531 did not. Time-course studies showed distinct kinetics of H1R gene upregulation in U-373 MG cells from that in HeLa cells. A promoter assay revealed that the promoter region responsible for H1R gene upregulation in U-373 MG cells was different from that of HeLa cells. These data suggest that the H1R-activated H1R gene expression signaling pathway in U-373 MG cells is different from that in HeLa cells, possibly by using different promoters. The involvement of PKCα also suggests that compounds that target PKCδ could work as peripheral type H1R-selective inhibitors without a sedative effect.

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