INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS
Search for new compounds providing delivery of drugs into infected or neoplastic cells, is an important direction of biomedical research. Cell-penetrating peptides are among those compounds, due to their ability to translocate through membranes of eukaryotic cells, serving as potential carriers of v...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists
2016-12-01
|
| Series: | Медицинская иммунология |
| Subjects: | |
| Online Access: | https://www.mimmun.ru/mimmun/article/view/1140 |
| _version_ | 1797197945208045568 |
|---|---|
| author | E. S. Umnyakova I. V. Kudryavtsev N. A. Grudinina S. V. Balandin I. A. Bolosov P. V. Panteleev T. A. Filatenkova D. S. Orlov E. V. Tsvetkova T. V. Ovchinnikova V. N. Kokryakov O. V. Shamova |
| author_facet | E. S. Umnyakova I. V. Kudryavtsev N. A. Grudinina S. V. Balandin I. A. Bolosov P. V. Panteleev T. A. Filatenkova D. S. Orlov E. V. Tsvetkova T. V. Ovchinnikova V. N. Kokryakov O. V. Shamova |
| author_sort | E. S. Umnyakova |
| collection | DOAJ |
| description | Search for new compounds providing delivery of drugs into infected or neoplastic cells, is an important direction of biomedical research. Cell-penetrating peptides are among those compounds, due to their ability to translocate through membranes of eukaryotic cells, serving as potential carriers of various therapeutic agents to the target cells. The aim of present work was to investigate the ability of acipensin 1, an antimicrobial peptide of innate immune system, for in vitro penetration into human tumor cells. Acipensin 1 is a cationic peptide that we have previously isolated from leukocytes of the Russian sturgeon, Acipenser gueldenstaedtii. Capability of acipensin 1 to enter the human erytroleukemia K-562 cells has been investigated for the first time. A biotechnological procedure for producing a recombinant acipensin 1 peptide has been developed. The obtained peptide was conjugated with a fluorescent probe BODIPY FL. By means of confocal microscopy, we have shown that the tagged acipensin 1 rapidly enters into K-562 cells and can be detected in the intracellular space within 5 min after its addition to the cell culture. Using flow cytometry technique, penetration kinetics of the labeled peptide into K-562 cells (at nontoxic micromolar concentrations) has been studied. We have observed a rapid internalization of the peptide to the target cells, thus confirming the results of microscopic analysis, i.e, the labeled acipensin was detectable in K-562 cells as soon as wihin 2-3 seconds after its addition to the incubation medium. The maximum of fluorescence was reached within a period of approx. 45 seconds, with further “plateau” at the terms of >100 seconds following cell stimulation with the test compound. These data support the concept, that the antimicrobial peptides of innate immunity system possess the features of cell-penetrating peptides, and allow us to consider the studied sturgeon peptide a promising template for development of new drugs with increased ability to enter the cells implicated into pathological processes, and, therefore, higher therapeutic efficiency. |
| first_indexed | 2024-03-08T05:49:38Z |
| format | Article |
| id | doaj.art-5ccd831982fb43eab004f22b2a8974db |
| institution | Directory Open Access Journal |
| issn | 1563-0625 2313-741X |
| language | Russian |
| last_indexed | 2024-04-24T06:52:01Z |
| publishDate | 2016-12-01 |
| publisher | St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists |
| record_format | Article |
| series | Медицинская иммунология |
| spelling | doaj.art-5ccd831982fb43eab004f22b2a8974db2024-04-22T13:07:41ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2016-12-0118657558210.15789/1563-0625-2016-6-575-582873INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLSE. S. Umnyakova0I. V. Kudryavtsev1N. A. Grudinina2S. V. Balandin3I. A. Bolosov4P. V. Panteleev5T. A. Filatenkova6D. S. Orlov7E. V. Tsvetkova8T. V. Ovchinnikova9V. N. Kokryakov10O. V. Shamova11Institute of Experimental Medicine, St. Petersburg, Russian FederationInstitute of Experimental Medicine, St. Petersburg, Russian Federation The First St. Petersburg I. Pavlov State Medical University, St. Petersburg, Russian FederationInstitute of Experimental Medicine, St. Petersburg, Russian FederationM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian FederationM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian FederationM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian FederationInstitute of Experimental Medicine, St. Petersburg, Russian FederationInstitute of Experimental Medicine, St. Petersburg, Russian FederationInstitute of Experimental Medicine, St. Petersburg, Russian FederationM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian FederationInstitute of Experimental Medicine, St. Petersburg, Russian Federation St. Petersburg State University, St. Petersburg, Russian FederationInstitute of Experimental Medicine, St. Petersburg, Russian Federation St. Petersburg State University, St. Petersburg, Russian FederationSearch for new compounds providing delivery of drugs into infected or neoplastic cells, is an important direction of biomedical research. Cell-penetrating peptides are among those compounds, due to their ability to translocate through membranes of eukaryotic cells, serving as potential carriers of various therapeutic agents to the target cells. The aim of present work was to investigate the ability of acipensin 1, an antimicrobial peptide of innate immune system, for in vitro penetration into human tumor cells. Acipensin 1 is a cationic peptide that we have previously isolated from leukocytes of the Russian sturgeon, Acipenser gueldenstaedtii. Capability of acipensin 1 to enter the human erytroleukemia K-562 cells has been investigated for the first time. A biotechnological procedure for producing a recombinant acipensin 1 peptide has been developed. The obtained peptide was conjugated with a fluorescent probe BODIPY FL. By means of confocal microscopy, we have shown that the tagged acipensin 1 rapidly enters into K-562 cells and can be detected in the intracellular space within 5 min after its addition to the cell culture. Using flow cytometry technique, penetration kinetics of the labeled peptide into K-562 cells (at nontoxic micromolar concentrations) has been studied. We have observed a rapid internalization of the peptide to the target cells, thus confirming the results of microscopic analysis, i.e, the labeled acipensin was detectable in K-562 cells as soon as wihin 2-3 seconds after its addition to the incubation medium. The maximum of fluorescence was reached within a period of approx. 45 seconds, with further “plateau” at the terms of >100 seconds following cell stimulation with the test compound. These data support the concept, that the antimicrobial peptides of innate immunity system possess the features of cell-penetrating peptides, and allow us to consider the studied sturgeon peptide a promising template for development of new drugs with increased ability to enter the cells implicated into pathological processes, and, therefore, higher therapeutic efficiency.https://www.mimmun.ru/mimmun/article/view/1140cell-penetrating peptidesantimicrobial peptidesacipensin 1 |
| spellingShingle | E. S. Umnyakova I. V. Kudryavtsev N. A. Grudinina S. V. Balandin I. A. Bolosov P. V. Panteleev T. A. Filatenkova D. S. Orlov E. V. Tsvetkova T. V. Ovchinnikova V. N. Kokryakov O. V. Shamova INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS Медицинская иммунология cell-penetrating peptides antimicrobial peptides acipensin 1 |
| title | INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS |
| title_full | INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS |
| title_fullStr | INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS |
| title_full_unstemmed | INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS |
| title_short | INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS |
| title_sort | internalization of antimicrobial peptide acipensin 1 into human tumor cells |
| topic | cell-penetrating peptides antimicrobial peptides acipensin 1 |
| url | https://www.mimmun.ru/mimmun/article/view/1140 |
| work_keys_str_mv | AT esumnyakova internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT ivkudryavtsev internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT nagrudinina internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT svbalandin internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT iabolosov internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT pvpanteleev internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT tafilatenkova internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT dsorlov internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT evtsvetkova internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT tvovchinnikova internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT vnkokryakov internalizationofantimicrobialpeptideacipensin1intohumantumorcells AT ovshamova internalizationofantimicrobialpeptideacipensin1intohumantumorcells |