The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation.
The BH3-only family member BNIP3 has been described as either promoting cell survival or cell death. This depends upon the level of BNIP3 expression and its cellular localization. Increased BNIP3 expression under hypoxia contributes to cell death through increased mitochondrial dysfunction. Furtherm...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6181300?pdf=render |
| _version_ | 1818926066117378048 |
|---|---|
| author | Amandeep Singh Meghan Azad Miriam D Shymko Elizabeth S Henson Sachin Katyal David D Eisenstat Spencer B Gibson |
| author_facet | Amandeep Singh Meghan Azad Miriam D Shymko Elizabeth S Henson Sachin Katyal David D Eisenstat Spencer B Gibson |
| author_sort | Amandeep Singh |
| collection | DOAJ |
| description | The BH3-only family member BNIP3 has been described as either promoting cell survival or cell death. This depends upon the level of BNIP3 expression and its cellular localization. Increased BNIP3 expression under hypoxia contributes to cell death through increased mitochondrial dysfunction. Furthermore, mice lacking BNIP3 show inhibition of ischemic cardiomyocyte apoptosis. In contrast, nuclear localization of BNIP3 contributes to blockage of apoptosis in glioma cells through repression of pro-apoptotic genes. We have discovered that mouse embryonic fibroblasts (MEFs) lacking BNIP3 expression show increased proliferation and cell number compared to wild-type cells. Furthermore, the cells lacking BNIP3 showed increased MAPK activation. Increased proliferation was not due to decreased cell death as oxidative stress induced cell death in BNIP3 null MEFs. In addition, we isolated astrocytes from wild-type or embryonic mice lacking expression of BNIP3. There was increased density and cell number in the astrocytes lacking BNIP3 expression. To confirm these results in human cells, we inducibly expressed BNIP3 in human embryonic kidney (HEK293) cells and found that induced BNIP3 reduced cell proliferation and failed to change background cell death levels. Transient over-expression of BNIP3 in the nucleus of HEK293 cells also reduced DNA synthesis. Finally, to determine whether this increased proliferation occurs in mice lacking BNIP3, we isolated brains from wild-type mice or those lacking BNIP3 expression. The mice lacking BNIP3 had increased cellularity in the brain of embryonic and adult mice. Taken together, our study describes a new function for BNIP3 in the regulation of cellular proliferation. |
| first_indexed | 2024-12-20T02:51:12Z |
| format | Article |
| id | doaj.art-279e629601cb48f3bc53e7333c5ad6ea |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:51:12Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-279e629601cb48f3bc53e7333c5ad6ea2022-12-21T19:56:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011310e020479210.1371/journal.pone.0204792The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation.Amandeep SinghMeghan AzadMiriam D ShymkoElizabeth S HensonSachin KatyalDavid D EisenstatSpencer B GibsonThe BH3-only family member BNIP3 has been described as either promoting cell survival or cell death. This depends upon the level of BNIP3 expression and its cellular localization. Increased BNIP3 expression under hypoxia contributes to cell death through increased mitochondrial dysfunction. Furthermore, mice lacking BNIP3 show inhibition of ischemic cardiomyocyte apoptosis. In contrast, nuclear localization of BNIP3 contributes to blockage of apoptosis in glioma cells through repression of pro-apoptotic genes. We have discovered that mouse embryonic fibroblasts (MEFs) lacking BNIP3 expression show increased proliferation and cell number compared to wild-type cells. Furthermore, the cells lacking BNIP3 showed increased MAPK activation. Increased proliferation was not due to decreased cell death as oxidative stress induced cell death in BNIP3 null MEFs. In addition, we isolated astrocytes from wild-type or embryonic mice lacking expression of BNIP3. There was increased density and cell number in the astrocytes lacking BNIP3 expression. To confirm these results in human cells, we inducibly expressed BNIP3 in human embryonic kidney (HEK293) cells and found that induced BNIP3 reduced cell proliferation and failed to change background cell death levels. Transient over-expression of BNIP3 in the nucleus of HEK293 cells also reduced DNA synthesis. Finally, to determine whether this increased proliferation occurs in mice lacking BNIP3, we isolated brains from wild-type mice or those lacking BNIP3 expression. The mice lacking BNIP3 had increased cellularity in the brain of embryonic and adult mice. Taken together, our study describes a new function for BNIP3 in the regulation of cellular proliferation.http://europepmc.org/articles/PMC6181300?pdf=render |
| spellingShingle | Amandeep Singh Meghan Azad Miriam D Shymko Elizabeth S Henson Sachin Katyal David D Eisenstat Spencer B Gibson The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation. PLoS ONE |
| title | The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation. |
| title_full | The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation. |
| title_fullStr | The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation. |
| title_full_unstemmed | The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation. |
| title_short | The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation. |
| title_sort | bh3 only bcl 2 family member bnip3 regulates cellular proliferation |
| url | http://europepmc.org/articles/PMC6181300?pdf=render |
| work_keys_str_mv | AT amandeepsingh thebh3onlybcl2familymemberbnip3regulatescellularproliferation AT meghanazad thebh3onlybcl2familymemberbnip3regulatescellularproliferation AT miriamdshymko thebh3onlybcl2familymemberbnip3regulatescellularproliferation AT elizabethshenson thebh3onlybcl2familymemberbnip3regulatescellularproliferation AT sachinkatyal thebh3onlybcl2familymemberbnip3regulatescellularproliferation AT daviddeisenstat thebh3onlybcl2familymemberbnip3regulatescellularproliferation AT spencerbgibson thebh3onlybcl2familymemberbnip3regulatescellularproliferation AT amandeepsingh bh3onlybcl2familymemberbnip3regulatescellularproliferation AT meghanazad bh3onlybcl2familymemberbnip3regulatescellularproliferation AT miriamdshymko bh3onlybcl2familymemberbnip3regulatescellularproliferation AT elizabethshenson bh3onlybcl2familymemberbnip3regulatescellularproliferation AT sachinkatyal bh3onlybcl2familymemberbnip3regulatescellularproliferation AT daviddeisenstat bh3onlybcl2familymemberbnip3regulatescellularproliferation AT spencerbgibson bh3onlybcl2familymemberbnip3regulatescellularproliferation |