Impact of Cyclin-Dependent Kinase CDK4 Inhibition on Eryptosis
Background/Aims: The cyclin-dependent kinase 4 (CDK4) participates in the regulation of apoptosis of nucleated cells by altering transcriptional regulation of genes governing cell proliferation and cell death. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, which is charac...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2015-09-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/430241 |
| _version_ | 1819296492013223936 |
|---|---|
| author | Elisabeth Lang Christine Zelenak Matthias Eberhard Rosi Bissinger Anand Rotte Mehrdad Ghashghaeinia Adrian Lupescu Florian Lang Syed M. Qadri |
| author_facet | Elisabeth Lang Christine Zelenak Matthias Eberhard Rosi Bissinger Anand Rotte Mehrdad Ghashghaeinia Adrian Lupescu Florian Lang Syed M. Qadri |
| author_sort | Elisabeth Lang |
| collection | DOAJ |
| description | Background/Aims: The cyclin-dependent kinase 4 (CDK4) participates in the regulation of apoptosis of nucleated cells by altering transcriptional regulation of genes governing cell proliferation and cell death. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at the cell surface. As mature erythrocytes lack nuclei, acute stimulation of eryptosis cannot result from altered gene expression. Eryptosis is triggered by isotonic cell shrinkage following Cl- removal (replacement with the impermeant organic anion gluconate) or by oxidative stress (exposure to 0.3 mM tertbutyl-hydroperoxide [tBOOH]). The present study explored whether CDK4 is expressed in erythrocytes and whether the CDK4 inhibitors II (NSC625987) and III (ryuvidine) influence eryptosis. Methods: Western blotting was utilized for determination of the presence of CDK4 protein in human erythrocytes, and FACS analysis to determine Fluo3 fluorescence (reflecting cytosolic Ca2+), annexin-V-binding (reflecting PS-exposure) and forward scatter (reflecting cell volume). Results: CDK4 protein was present in human erythrocytes. Cl- removal was followed by decrease of forward scatter and increase of both annexin-V-binding and Fluo3 fluorescence, an effect significantly curtailed by CDK4 inhibitors II and III. Furthermore, CDK4 inhibition blunted enhanced PS-exposure elicited by tBOOH treatment. Conclusions: The present observations disclose the presence of CDK4 protein in human erythrocytes and the suppression of suicidal erythrocyte death by pharmacological inhibition of CDK4. |
| first_indexed | 2024-12-24T04:58:58Z |
| format | Article |
| id | doaj.art-7b2c67301b5349a9bf860faa43c6d6b5 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-24T04:58:58Z |
| publishDate | 2015-09-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-7b2c67301b5349a9bf860faa43c6d6b52022-12-21T17:14:17ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-09-013731178118610.1159/000430241430241Impact of Cyclin-Dependent Kinase CDK4 Inhibition on EryptosisElisabeth LangChristine ZelenakMatthias EberhardRosi BissingerAnand RotteMehrdad GhashghaeiniaAdrian LupescuFlorian LangSyed M. QadriBackground/Aims: The cyclin-dependent kinase 4 (CDK4) participates in the regulation of apoptosis of nucleated cells by altering transcriptional regulation of genes governing cell proliferation and cell death. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at the cell surface. As mature erythrocytes lack nuclei, acute stimulation of eryptosis cannot result from altered gene expression. Eryptosis is triggered by isotonic cell shrinkage following Cl- removal (replacement with the impermeant organic anion gluconate) or by oxidative stress (exposure to 0.3 mM tertbutyl-hydroperoxide [tBOOH]). The present study explored whether CDK4 is expressed in erythrocytes and whether the CDK4 inhibitors II (NSC625987) and III (ryuvidine) influence eryptosis. Methods: Western blotting was utilized for determination of the presence of CDK4 protein in human erythrocytes, and FACS analysis to determine Fluo3 fluorescence (reflecting cytosolic Ca2+), annexin-V-binding (reflecting PS-exposure) and forward scatter (reflecting cell volume). Results: CDK4 protein was present in human erythrocytes. Cl- removal was followed by decrease of forward scatter and increase of both annexin-V-binding and Fluo3 fluorescence, an effect significantly curtailed by CDK4 inhibitors II and III. Furthermore, CDK4 inhibition blunted enhanced PS-exposure elicited by tBOOH treatment. Conclusions: The present observations disclose the presence of CDK4 protein in human erythrocytes and the suppression of suicidal erythrocyte death by pharmacological inhibition of CDK4.http://www.karger.com/Article/FullText/430241ApoptosisEryptosisCell shrinkageCalciumCDK4 |
| spellingShingle | Elisabeth Lang Christine Zelenak Matthias Eberhard Rosi Bissinger Anand Rotte Mehrdad Ghashghaeinia Adrian Lupescu Florian Lang Syed M. Qadri Impact of Cyclin-Dependent Kinase CDK4 Inhibition on Eryptosis Cellular Physiology and Biochemistry Apoptosis Eryptosis Cell shrinkage Calcium CDK4 |
| title | Impact of Cyclin-Dependent Kinase CDK4 Inhibition on Eryptosis |
| title_full | Impact of Cyclin-Dependent Kinase CDK4 Inhibition on Eryptosis |
| title_fullStr | Impact of Cyclin-Dependent Kinase CDK4 Inhibition on Eryptosis |
| title_full_unstemmed | Impact of Cyclin-Dependent Kinase CDK4 Inhibition on Eryptosis |
| title_short | Impact of Cyclin-Dependent Kinase CDK4 Inhibition on Eryptosis |
| title_sort | impact of cyclin dependent kinase cdk4 inhibition on eryptosis |
| topic | Apoptosis Eryptosis Cell shrinkage Calcium CDK4 |
| url | http://www.karger.com/Article/FullText/430241 |
| work_keys_str_mv | AT elisabethlang impactofcyclindependentkinasecdk4inhibitiononeryptosis AT christinezelenak impactofcyclindependentkinasecdk4inhibitiononeryptosis AT matthiaseberhard impactofcyclindependentkinasecdk4inhibitiononeryptosis AT rosibissinger impactofcyclindependentkinasecdk4inhibitiononeryptosis AT anandrotte impactofcyclindependentkinasecdk4inhibitiononeryptosis AT mehrdadghashghaeinia impactofcyclindependentkinasecdk4inhibitiononeryptosis AT adrianlupescu impactofcyclindependentkinasecdk4inhibitiononeryptosis AT florianlang impactofcyclindependentkinasecdk4inhibitiononeryptosis AT syedmqadri impactofcyclindependentkinasecdk4inhibitiononeryptosis |