Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines.
CD47 activation through the C-terminus of thrombospondin-1 or its derived peptides (4N1K and PKHB1) induce regulated cell death (RCD) in several types of cancer. Recently, it was demonstrated that PKHB1, the first serum-stable CD47 agonist peptide, induce caspase-independent, calcium-dependent RCD i...
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| Format: | Tesis |
| Language: | English |
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2017
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| Online Access: | http://eprints.uanl.mx/14460/1/1080252237.pdf |
| _version_ | 1824348541804347392 |
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| author | Gómez Morales, Luis |
| author_facet | Gómez Morales, Luis |
| author_sort | Gómez Morales, Luis |
| collection | Tesis |
| description | CD47 activation through the C-terminus of thrombospondin-1 or its derived peptides (4N1K and PKHB1) induce regulated cell death (RCD) in several types of cancer. Recently, it was demonstrated that PKHB1, the first serum-stable CD47 agonist peptide, induce caspase-independent, calcium-dependent RCD in CLL cells, even in those resistant to conventional therapy. Therefore, the objective of the present work was to study the PKHB1-induced cell death mechanism in other types of leukemia. To that end, cell death induction was evaluated by flow cytometry, analyzing phosphatidilserine exposure (Ann-V) and plasma membrane permeability (PI), as well as caspase dependance (inhibitor Q-VD-OPH) or calcium dependance (BAPTA, calcium chelator). The results show that PKHB1 is a better inductor of cell death, compared to 4N1K, and it is selective to different types of leukemia (MEC-1, CEM, Junket, K562, HL-60, L5178Y-R), since it does not kill human peripheral mononuclear cells, nor cells derived from lymphoid organs of healthy mice. PKHB1-induced killing is caspase-independent in all cases.
Additionally, in CEM (human T lymphoblasts of acute lymphocytic leukemia, the principal type of childhood cancer) and L5178Y-R (murine T lymphoblasts) cells, death is not modulated by co-culture with chemoprotective bone marrow stromal cells; calcium chelation, however, inhibits PKHB1-induced cell death. Together, the results indicate that PKHB1 is effective in different types of leukemia, and induce caspase-independent, microenvironment-independent calcium-dependent RCD, in leukemic T lymphocytes. These results suggest that PKHB1-induced RCD could be conserved in different types of leukemia, and set the basis for further studies on murine models. |
| first_indexed | 2025-02-06T03:21:59Z |
| format | Tesis |
| id | eptesis-14460 |
| institution | UANL |
| language | English |
| last_indexed | 2025-02-06T03:21:59Z |
| publishDate | 2017 |
| record_format | eprints |
| spelling | eptesis-144602019-12-03T17:14:50Z http://eprints.uanl.mx/14460/ Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. Gómez Morales, Luis CD47 activation through the C-terminus of thrombospondin-1 or its derived peptides (4N1K and PKHB1) induce regulated cell death (RCD) in several types of cancer. Recently, it was demonstrated that PKHB1, the first serum-stable CD47 agonist peptide, induce caspase-independent, calcium-dependent RCD in CLL cells, even in those resistant to conventional therapy. Therefore, the objective of the present work was to study the PKHB1-induced cell death mechanism in other types of leukemia. To that end, cell death induction was evaluated by flow cytometry, analyzing phosphatidilserine exposure (Ann-V) and plasma membrane permeability (PI), as well as caspase dependance (inhibitor Q-VD-OPH) or calcium dependance (BAPTA, calcium chelator). The results show that PKHB1 is a better inductor of cell death, compared to 4N1K, and it is selective to different types of leukemia (MEC-1, CEM, Junket, K562, HL-60, L5178Y-R), since it does not kill human peripheral mononuclear cells, nor cells derived from lymphoid organs of healthy mice. PKHB1-induced killing is caspase-independent in all cases. Additionally, in CEM (human T lymphoblasts of acute lymphocytic leukemia, the principal type of childhood cancer) and L5178Y-R (murine T lymphoblasts) cells, death is not modulated by co-culture with chemoprotective bone marrow stromal cells; calcium chelation, however, inhibits PKHB1-induced cell death. Together, the results indicate that PKHB1 is effective in different types of leukemia, and induce caspase-independent, microenvironment-independent calcium-dependent RCD, in leukemic T lymphocytes. These results suggest that PKHB1-induced RCD could be conserved in different types of leukemia, and set the basis for further studies on murine models. 2017 Tesis NonPeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/14460/1/1080252237.pdf http://eprints.uanl.mx/14460/1.haspreviewThumbnailVersion/1080252237.pdf Gómez Morales, Luis (2017) Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. Maestría thesis, Universidad Autónoma de Nuevo León. |
| spellingShingle | Gómez Morales, Luis Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/tesis.png |
| title | Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. |
| title_full | Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. |
| title_fullStr | Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. |
| title_full_unstemmed | Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. |
| title_short | Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. |
| title_sort | study of the mechanism of cell death caused by peptides targeting cd47 in leukemia cell lines |
| url | http://eprints.uanl.mx/14460/1/1080252237.pdf |
| work_keys_str_mv | AT gomezmoralesluis studyofthemechanismofcelldeathcausedbypeptidestargetingcd47inleukemiacelllines |