scholarly journals Essential role of obscurin in cardiac myofibrillogenesis and hypertrophic response: evidence from small interfering RNA-mediated gene silencing

2005 ◽  
Vol 125 (3) ◽  
pp. 227-238 ◽  
Author(s):  
Andrei B. Borisov ◽  
Sarah B. Sutter ◽  
Aikaterini Kontrogianni-Konstantopoulos ◽  
Robert J. Bloch ◽  
Margaret V. Westfall ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Small Interfering Rna ◽  
Essential Role ◽  
Hypertrophic Response ◽  
Interfering Rna

scholarly journals An AP-1/clathrin coat plays a novel and essential role in forming the Weibel-Palade bodies of endothelial cells

2005 ◽  
Vol 170 (4) ◽  
pp. 627-636 ◽  
Author(s):  
Winnie W.Y. Lui-Roberts ◽  
Lucy M. Collinson ◽  
Lindsay J. Hewlett ◽  
Grégoire Michaux ◽  
Daniel F. Cutler
Keyword(s):  
Endothelial Cells ◽  
Small Interfering Rna ◽  
Essential Role ◽  
Secretory Granules ◽  
Transport Vesicles ◽  
Truncation Mutant ◽  
Golgi Network ◽  
Interfering Rna ◽  
Selective Aggregation

Clathrin provides an external scaffold to form small 50–100-nm transport vesicles. In contrast, formation of much larger dense-cored secretory granules is driven by selective aggregation of internal cargo at the trans-Golgi network; the only known role of clathrin in dense-cored secretory granules formation is to remove missorted proteins by small, coated vesicles during maturation of these spherical organelles. The formation of Weibel-Palade bodies (WPBs) is also cargo driven, but these are cigar-shaped organelles up to 5 μm long. We hypothesized that a cytoplasmic coat might be required to make these very different structures, and we found that new and forming WPBs are extensively, sometimes completely, coated. Overexpression of an AP-180 truncation mutant that prevents clathrin coat formation or reduced AP-1 expression by small interfering RNA both block WPB formation. We propose that, in contrast to other secretory granules, cargo aggregation alone is not sufficient to form immature WPBs and that an external scaffold that contains AP-1 and clathrin is essential.

Targeted Gene Silencing by Small Interfering RNA-Based Knock-Down Technology

2004 ◽  
Vol 5 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Bentham Science Publisher Zhang J. ◽  
Bentham Science Publisher Hua Z.C.
Keyword(s):  
Gene Silencing ◽  
Small Interfering Rna ◽  
Knock Down ◽  
Interfering Rna

scholarly journals Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanism

2011 ◽  
Vol 301 (3) ◽  
pp. H903-H911 ◽  
Author(s):  
Kanchana Karuppiah ◽  
Lawrence J. Druhan ◽  
Chun-an Chen ◽  
Travis Smith ◽  
Jay L. Zweier ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Oxidase Activity ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Caveolin 1 ◽  
Calcium Calmodulin Dependent ◽  
Enos Uncoupling ◽  
Nadph Oxidation ◽  
Interfering Rna

In the vasculature, nitric oxide (NO) is generated by endothelial NO synthase (eNOS) in a calcium/calmodulin-dependent reaction. In the absence of the requisite eNOS cofactor tetrahydrobiopterin (BH4), NADPH oxidation is uncoupled from NO generation, leading to the production of superoxide. Although this phenomenon is apparent with purified enzyme, cellular studies suggest that formation of the BH4 oxidation product, dihydrobiopterin, is the molecular trigger for eNOS uncoupling rather than BH4 depletion alone. In the current study, we investigated the effects of both BH4 depletion and oxidation on eNOS-derived superoxide production in endothelial cells in an attempt to elucidate the molecular mechanisms regulating eNOS oxidase activity. Results demonstrated that pharmacological depletion of endothelial BH4 does not result in eNOS oxidase activity, whereas BH4 oxidation gave rise to significant eNOS-oxidase activity. These findings suggest that the endothelium possesses regulatory mechanisms, which prevent eNOS oxidase activity from pterin-free eNOS. Using a combination of gene silencing and pharmacological approaches, we demonstrate that eNOS-caveolin-1 association is increased under conditions of reduced pterin bioavailability and that this sequestration serves to suppress eNOS uncoupling. Using small interfering RNA approaches, we demonstrate that caveolin-1 gene silencing increases eNOS oxidase activity to 85% of that observed under conditions of BH4 oxidation. Moreover, when caveolin-1 silencing was combined with a pharmacological inhibitor of AKT, BH4 depletion increased eNOS-derived superoxide to 165% of that observed with BH4 oxidation. This study identifies a critical role of caveolin-1 in the regulation of eNOS uncoupling and provides new insight into the mechanisms through which disease-associated changes in caveolin-1 expression may contribute to endothelial dysfunction.

Pre-Injection of Small Interfering RNA (siRNA) Promotes c-Jun Gene Silencing and Decreases the Survival Rate of Axotomy-Injured Spinal Motoneurons in Adult Mice

2018 ◽  
Vol 65 (3) ◽  
pp. 400-410 ◽  
Author(s):  
Ying-qin Li ◽  
Fa-huan Song ◽  
Ke Zhong ◽  
Guang-yin Yu ◽  
Prince Last Mudenda Zilundu ◽  
...  
Keyword(s):  
Survival Rate ◽  
Gene Silencing ◽  
Small Interfering Rna ◽  
Spinal Motoneurons ◽  
Adult Mice ◽  
Interfering Rna

scholarly journals Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2637
Author(s):  
Joon Min Jung ◽  
Tai Kyung Noh ◽  
Soo Youn Jo ◽  
Su Yeon Kim ◽  
Youngsup Song ◽  
...  
Keyword(s):  
Stem Cell Factor ◽  
Small Interfering Rna ◽  
Skin Pigmentation ◽  
Epidermal Keratinocytes ◽  
Melanin Content ◽  
Human Epidermal Keratinocytes ◽  
Guanine Deaminase ◽  
Keratinocyte Culture ◽  
Interfering Rna

Epidermal keratinocytes are considered as the most important neighboring cells that modify melanogenesis. Our previous study used microarray to show that guanine deaminase (GDA) gene expression is highly increased in melasma lesions. Hence, we investigated the role of GDA in skin pigmentation. We examined GDA expression in post-inflammatory hyperpigmentation (PIH) lesions, diagnosed as Riehl’s melanosis. We further investigated the possible role of keratinocyte-derived GDA in melanogenesis by quantitative PCR, immunofluorescence staining, small interfering RNA-based GDA knockdown, and adenovirus-mediated GDA overexpression. We found higher GDA positivity in the hyperpigmentary lesional epidermis than in the perilesional epidermis. Both UVB irradiation and stem cell factor (SCF) plus endothelin-1 (ET-1) were used, which are well-known melanogenic stimuli upregulating GDA expression in both keratinocyte culture alone and keratinocyte and melanocyte coculture. GDA knockdown downregulated melanin content, while GDA overexpression promoted melanogenesis in the coculture. When melanocytes were treated with UVB-exposed keratinocyte-conditioned media, the melanin content was increased. Also, GDA knockdown lowered SCF and ET-1 expression levels in keratinocytes. GDA in epidermal keratinocytes may promote melanogenesis by upregulating SCF and ET-1, suggesting its role in skin hyperpigmentary disorders.

scholarly journals Essential role of Drosophila Hdac1 in homeotic gene silencing

2001 ◽  
Vol 98 (17) ◽  
pp. 9730-9735 ◽  
Author(s):  
Y.-L. Chang ◽  
Y.-H. Peng ◽  
I.-C. Pan ◽  
D.-S. Sun ◽  
B. King ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Essential Role ◽  
Homeotic Gene

scholarly journals Functional Analysis of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Differentially Expressed by Variants of Human HT-1080 Fibrosarcoma Exhibiting High and Low Levels of Intravasation and Metastasis

2007 ◽  
Vol 282 (49) ◽  
pp. 35964-35977 ◽  
Author(s):  
Juneth J. Partridge ◽  
Mark A. Madsen ◽  
Veronica C. Ardi ◽  
Thales Papagiannakopoulos ◽  
Tatyana A. Kupriyanova ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Cancer Cell ◽  
Small Interfering Rna ◽  
Cultured Cells ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Down Regulation ◽  
Primary Tumors ◽  
Tissue Inhibitors ◽  
Interfering Rna

The role of tumor-derived matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in cancer cell dissemination was analyzed by employing two variants of human HT-1080 fibrosarcoma, HT-hi/diss and HT-lo/diss, which differ by 50-100-fold in their ability to intravasate and metastasize in the chick embryo. HT-hi/diss and HT-lo/diss were compared by quantitative reverse transcription-PCR and Western blot analyses for mRNA and protein expression of nine MMPs (MMP-1, -2, -3, -7, -8, -9, -10, -13, and -14) and three TIMPs (TIMP-1, -2, and -3) in cultured cells in vitro and in primary tumors in vivo. MMP-1 and MMP-9 were more abundant in the HT-hi/diss variant, both in cultures and in tumors, whereas the HT-lo/diss variant consistently expressed higher levels of MMP-2, TIMP-1, and TIMP-2. Small interfering RNA-mediated down-regulation of MMP-2 and TIMP-2 increased intravasation of HT-lo/diss cells. Coordinately, treatment of the developing HT-hi/diss tumors with recombinant TIMP-1 and TIMP-2 significantly reduced HT-hi/diss cell intravasation. However, a substantial increase of HT-hi/diss dissemination was observed upon small interfering RNA-mediated down-regulation of three secreted MMPs, including the interstitial collagenase MMP-1 and the two gelatinases, MMP-2 and MMP-9, but not the membrane-tethered MMP-14. The addition of recombinant pro-MMP-9 protein to the HT-hi/diss tumors reversed the increased intravasation of HT-hi/diss cells, in which MMP-9 was stably down-regulated by short hairpin RNA interference. This rescue did not occur if the pro-MMP-9 was stoichiometrically complexed with TIMP-1, pointing to a direct role of the MMP-9 enzyme in regulation of HT-hi/diss intravasation. Collectively, these findings demonstrate that tumor-derived MMPs may have protective functions in cancer cell intravasation, i.e. not promoting but rather catalytically interfering with the early stages of cancer dissemination.

scholarly journals Elucidating the role of surface chemistry on cationic phosphorus dendrimer–siRNA complexation

Nanoscale ◽  
2018 ◽  
Vol 10 (23) ◽  
pp. 10952-10962 ◽  
Author(s):  
Marco A. Deriu ◽  
Nicolas Tsapis ◽  
Magali Noiray ◽  
Gianvito Grasso ◽  
Nabil El Brahmi ◽  
...  
Keyword(s):  
Surface Chemistry ◽  
Structural Properties ◽  
Crucial Role ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Interfering Rna

In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the surface chemistry, play a crucial role in the efficiency of complexation.

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