Intranuclear targeted delivery of functional NF-kappa B by 70kDa heatshock protein

Fujihara, Sheri M.; Nadler, Steven G.

doi:10.1093/emboj/18.2.411

Cited by 61 publications

(40 citation statements)

References 25 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether such receptors exist and bind Hsp70 in neurons has not been investigated. However, in addition to such receptor-mediated activity, there is evidence that HSP70 can be internalized and readily imported into both cytoplasmic and nuclear compartments of arterial smooth muscle cells, U937 cells, lymphocytes, retinal ganglion cells, and neuroblastoma cells (Johnson et al, 1990(Johnson et al, , 1995Guzhova et al, 1998;Fujihara and Nadler, 1999;Guzhova et al, 2001;Yu et al, 2001). Administration of e-rhHsp70 reduces the number of dying motoneurons in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Although the best understood role of HSP70 relates to its intracellular functions, secretion or release of HSP70 by one cell population to act on neighboring cells has been suggested (Tytell et al, 1986;Hightower and Guidon, 1989;Guzhova et al, 2001). Although it is unclear how extracellular Hsps function, there is evidence that they can be internalized and readily imported into both cytoplasmic and nuclear compartments of many cell types and that they appear to promote survival (Johnson et al, 1990(Johnson et al, , 1995Houenou et al, 1996;Guzhova et al, 1998;Fujihara and Nadler, 1999;Yu et al, 2001;Tidwell et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival

Robinson¹,

Tidwell²,

Gould³

et al. 2005

J. Neurosci.

111

View full text Add to dashboard Cite

The dependence of developing spinal motoneuron survival on a soluble factor(s) from their target, muscle tissue is well established both in vivo and in vitro. Considering this apparent dependence, we examined whether a specific component of the stress response mediates motoneuron survival in trophic factor-deprived environments. We demonstrate that, although endogenous expression of heat shock protein 70 (HSP70) did not change during trophic factor deprivation, application of e-rhHsp70 (exogenous recombinant human Hsp70) promoted motoneuron survival. Conversely, depletion of HSP70 from chick muscle extract (MEx) potently reduces the survivalpromoting activity of MEx. Additionally, exogenous treatment with or spinal cord overexpression of Hsp70 enhances motoneuron survival in vivo during the period of naturally occurring cell death [programmed cell death (PCD)]. Hindlimb muscle cells and lumbar spinal astrocytes readily secrete HSP70 in vitro, suggesting potential physiological sources of extracellular Hsp70 for motoneurons. However, in contrast to exogenous treatment with or overexpression of Hsp70 in vivo, muscle-targeted injections of this factor in an ex vivo preparation fail to attenuate motoneuron PCD. These data (1) suggest that motoneuron survival requirements may extend beyond classical trophic factors to include HSP70, (2) indicate that the source of this factor is instrumental in determining its trophic function, and (3) may therefore influence therapeutic strategies designed to increase motoneuron Hsp70 signaling during disease or injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival

Robinson¹,

Tidwell²,

Gould³

et al. 2005

J. Neurosci.

111

View full text Add to dashboard Cite

show abstract

“…Fujihara and Nadler (1999) showed that exogenous Hsp70s enter certain cells and transport the proteins to nuclei. Schemes to exploit BER enhancement would not be difficult to imagine.…”

Section: Stress-induced Apoptosis Is Influenced By Hsp70mentioning

confidence: 99%

Clonogenicity of human leukemic cells protected from cell-lethal agents by heat shock protein 70

Bases

2005

Cell Stress Chaper

View full text Add to dashboard Cite

Pretreatment of human leukemia THP-1 cells with heat shock protein Hsp70 (Hsp70) protected them from the cell-lethal effects of the topoisomerase II inhibitor, lucanthone and from ionizing radiation. Cell viability was scored in clonogenic assays of single cells grown in liquid medium containing 0.5% methyl cellulose. Colonies were observed and rapidly scored after staining with the tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide. The frequency of abasic sites in the deoxyribonucleic acid (DNA) of THP-1 cells was reduced when these cells were treated with Hsp70. Hsp70 is presumed to have protected the cells by promoting repair of cell DNA, in agreement with previous studies that showed that Hsp70 enhanced base excision repair by purified enzymes. The shoulders of radiation dose-response curves were enhanced by pretreatment of cells with Hsp70 and, importantly, were reduced when cells were transfected with ribonucleic acid designed to silence Hsp70. Hsp70 influenced repair of sublethal damage after radiation.

show abstract

“…Similarly, the same peptide delivered with a different PTD (PTD-5) blocked the adverse effects of the pro-inflammatory cytokine IL-1β on islet cell function [49]. Finally, combinations of hydrophobic and nuclear localization sequence (NLS) peptides have been used to inhibit nuclear translocation of NF-κB [50][51][52].…”

Section: Introduction Of Heterologous Proteins Using Ptdsmentioning

confidence: 99%

Biological applications of protein transduction technology

Kabouridis

2003

Trends in Biotechnology

View full text Add to dashboard Cite

The impermeable nature of the cell membrane to peptides, proteins, DNA and oligonucleotides limits the therapeutic potential of these biological agents. However, the recent discovery of short cationic peptides that cross the plasma membrane efficiently is opening up new possibilities for the intracellular delivery of such agents. These peptides are commonly referred to as protein transduction domains (PTDs) and are successfully used to transport heterologous proteins, peptides and other types of cargo into cells. Several recent reports have used the membrane transducing technology in vivo to deliver biologically active cargo into various tissues. This review discusses the structure of the most commonly used PTDs and how their ability to transduce membranes is used to regulate biological functions. It also considers future directions and the potential of this technology to move from the laboratory into the clinic.Defining the function of a protein or controlling its action requires cellular expression of mutant forms of the protein or silencing of the corresponding gene. Until recently, this was achieved by transgene expression, either using recombinant vectors or directly introducing proteins into cells by microinjection, electroporation or red-cell ghost fusion, all of which are cumbersome techniques requiring specialist equipment [1][2][3]. Now, a new, non-invasive technology for the direct delivery of biological material is emerging, following the discovery that certain proteins can enter cells in an unconventional way. The TAT protein, a transactivation factor from the human immunodeficiency virus 1 (HIV-1), was the first polypeptide shown to gain entry into cells when added exogenously to culture medium [4][5][6]. Other proteins reported to cross the plasma membrane belong to the homeoprotein family of transcription factors [7] such as the Drosophila Antennapedia (Antp) protein [7,8].The herpes simplex virus VP22 has also been reported to cross the plasma membrane [9], although this result has recently been questioned [10]. The subsequent identification of short membrane-permeable cationic peptides derived from these proteins, and synthesis of other amphipathic peptides such as transportan [11,12], MAP [13] and KALA [14], has led to the development of a new technology for delivering biological agents into cells. These peptides are commonly known as protein transduction domains (PTDs) [15,16] or cell-penetrating peptides [17][18][19]. Hydrophobic domains corresponding to the leader sequence of proteins also cross membranes and have been used to introduce bioactive peptides into cells [20,21]. However, they might not be as potent as cationic PTDs and are only briefly mentioned here. At present, how membrane-transducing proteins and peptide transporters are internalized is not clearly understood. Initially, internalization was reported to take place at 4°C and in the presence of endocytosis inhibitors, suggesting that these peptides do not use the conventional endocytic pathway to enter cells [8,27,28,...

show abstract

Intranuclear targeted delivery of functional NF-kappa B by 70kDa heatshock protein

Cited by 61 publications

References 25 publications

Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival

Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival

Clonogenicity of human leukemic cells protected from cell-lethal agents by heat shock protein 70

Biological applications of protein transduction technology

Contact Info

Product

Resources

About