Blood pressure modulation following activation of mast cells by cationic cell penetrating peptides |
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| Affiliation: | 1. Laboratory of Biotechnology and Radiobiology, Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;2. Cardiothoracic and Thoracic Research Center, Department of Cardiothoracic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;3. The Laboratory of Allergy and Clinical Immunology, Meir Medical Center, Kfar Saba, Israel;4. Sackler School of Medicine, Tel Aviv University, Israel;1. Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia;2. Graduate School of Biomedicine, University of Ljubljana, Ljubljana 1000, Slovenia;3. Doctoral Programme in Chemical Sciences, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana 1000, Slovenia;4. Laboratory for Materials Chemistry, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia;5. EN-FIST, Centre of Excellence, Trg Osvobodilne fronte 13, Ljubljana 1000, Slovenia;1. Interfacultary Research Center of Biomaterials, University of Liège, Institute of Chemistry, Building B6C, Sart-Tilman, Liège 4000, Belgium;2. Laboratory of Thrombosis and Haemostasis, GIGA-Cardiovascular Sciences, University of Liège, Belgium;1. Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200, Copenhagen, Denmark;2. Dansk Fundamental Metrologi, Matematiktorvet 307, DK-2600, Lyngby, Denmark;1. Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China;2. The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350005, China;1. Department of Medicine, University of Virginia, Charlottesville, Va;2. Division of Cardiology, University of Virginia, Charlottesville, Va;3. Houston Methodist DeBakey Heart & Vascular Center, Houston, Tex;4. Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Va;5. The Carter Center for Immunology, University of Virginia, Charlottesville, Va |
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| Abstract: | Short cell penetrating peptides (CPP) are widely used in vitro to transduce agents into cells. But their systemic effect has not been yet studied in detail. We studied the systemic effect of the cell penetrating peptides, penetratin, transportan and pro-rich, on rat hemodynamic functions. Intra-arterial monitoring of blood pressure showed that injection of the positively charged penetratin and transportan in a wide range of concentrations (2.5–320 μg/kg) caused highly significant transient decrease in the systolic and diastolic blood pressure in a dose dependent manner (p < 0.01). Pretreatment with histamine receptors blockers or with cromolyn, a mast cell stabilizing agent, significantly attenuated this effect. Furthermore, in vitro incubation of these both peptides with mast cells line, LAD2, caused a massive mast cell degranulation. In vitro studies showed that these CPP in a wide range of concentrations were not cytotoxic without any effect on the survival of LAD2 mast cell line. In contrast, the less positively charged and proline-rich CPP, pro-rich, had no systemic effects with no effect on mast cell degranulation. Our results indicate that intravenously administrated positively charged CPP may have deleterious consequences due to their induced BP drop, mediated by mast cell activation. Therefore, the major effect of mast cell activation on BP should be considered in developing possible future drug therapies based on the injection of membrane-permeable and positively charged CPP. Nevertheless, lower levels of such CPP may be considered as a treatment of systemic high BP through moderate systemic mast cell activation. |
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