Anemia and splenomegaly in cGKI-deficient mice
Open accessAbstract
To explore the functional significance of cGMP-dependent protein kinase type I (cGKI) in the regulation of erythrocyte survival, gene-targeted mice lacking cGKI were compared with their control littermates. By the age of 10 weeks, cGKI-deficient mice exhibited pronounced anemia and splenomegaly. Compared with control mice, the cGKI mutants had significantly lower red blood cell count, packed cell volume, and hemoglobin concentration. Anemia was associated with a higher reticulocyte number and an increase of plasma erythropoietin concentration. The spleens of cGKI mutant mice were massively enlarged and contained a higher fraction of Ter119 + erythroid cells, whereas the relative proportion of leukocyte subpopulations was not changed. The Ter119 + cGKI-deficient splenocytes showed a marked increase in annexin V binding, pointing to phosphatidylserine (PS) exposure at the outer membrane leaflet, a hallmark of suicidal erythrocyte death or eryptosis. Compared with control erythrocytes, cGKI-deficient erythrocytes exhibited in vitro a higher cytosolic Ca 2+ concentration, a known trigger of eryptosis, and showed increased PS exposure, which was paralleled by a faster clearance in vivo . Together, these results identify a role of cGKI as mediator of erythrocyte survival and extend the emerging concept that cGMP/cGKI signaling has an antiapoptotic/prosurvival function in a number of cell types in vivo .
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Loss of RBCs due to acute or chronic bleeding is another important cause of anemia.
“Another important cause of anemia is the loss of RBCs due to acute or chronic bleeding (59).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [59]
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- Authors
- Föller, M., Feil, S., Ghoreschi, K., Koka, S., Gerling, A., Thunemann, M., Hofmann, F., Schuler, B., Vogel, J., Pichler, B., Kasinathan, R. S., Nicolay, J. P., Huber, S. M., Lang, F., & Feil, R.
- Affiliations
- *Department of Physiology,
- Interfakultäres Institut für Biochemie,
- Departments of ‡Dermatology and
- Technical University of Munich (DE)
- University of Zurich (CH)
- University of Tübingen (DE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-05-06
- Volume
- 105
- Issue
- 18
- Pages
- 6771-6776
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2373362
- OpenAlex
- W1980548122
- Cited by
- 136
- References
- 60
- Citations by year
- 2025: 2 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 9 · 2015: 15 · 2014: 21 · 2013: 25 · 2012: 16
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- cGMP-dependent protein kinase I, anemia, splenomegaly, erythrocyte survival, eryptosis, erythrocyte apoptosis, erythropoietin, reticulocytes, phosphatidylserine exposure, annexin V binding, intracellular calcium, erythroid cells, cGMP signaling, gene-targeted mice
- MeSH terms
- Anemia, Animals, Calcium, Erythrocytes, Fluoresceins, Splenomegaly, Succinimides, Cyclic GMP-Dependent Protein Kinases, Intracellular Space, Cell Size, Mice, Cyclic GMP-Dependent Protein Kinase Type I
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