Stress-specific responses of p21 expression: Implication of transcript variant p21 alt-a in long-term hypoxia

p21 (CDKN1A, Cip1, Waf1) is a cyclin‐dependent kinase inhibitor capable of causing cell cycle arrest or promoting cell cycle transit as well as acting as a regulator of apoptosis. In this study, we analyzed the effects of various antemortem conditions on p21 protein level and expression profiles of...

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Published in:Journal of cellular biochemistry 2012-02, Vol.113 (2), p.544-552
Main Authors: Kaija, Helena M., Särkioja, Terttu, Kortelainen, Marja-Leena, Vuoristo, Jussi T., Huikuri, Heikki V., Porvari, Katja S.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
APOPTOSIS
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - metabolism
CARDIOPROTECTION
Cause of Death
CELL CYCLE TRANSIT
Cell Nucleus - metabolism
Cyclin-Dependent Kinase Inhibitor p21 - genetics
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Female
Humans
HYPOTHERMIA
Hypothermia - metabolism
HYPOXIA
Hypoxia - metabolism
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Male
Middle Aged
Muscle, Smooth, Vascular - pathology
Myocardial Ischemia - metabolism
Myocardium - metabolism
Myocardium - pathology
Myocytes, Cardiac - metabolism
Myocytes, Smooth Muscle - metabolism
p21
Protein Isoforms - genetics
Protein Isoforms - metabolism
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Proto-Oncogene Proteins c-pim-1 - genetics
Proto-Oncogene Proteins c-pim-1 - metabolism
Real-Time Polymerase Chain Reaction
Stress, Physiological
Transcription, Genetic
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Young Adult
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Summary:p21 (CDKN1A, Cip1, Waf1) is a cyclin‐dependent kinase inhibitor capable of causing cell cycle arrest or promoting cell cycle transit as well as acting as a regulator of apoptosis. In this study, we analyzed the effects of various antemortem conditions on p21 protein level and expression profiles of known p21 transcript variants in human heart tissue. The selected death cause groups were: non‐cardiac, hypothermia, acute ischemia, and chronic hypoxia. Immunohistochemical staining of p21 in cardiac myocytes could be observed only in hypothermia death cases, in which the mRNA expression of the most abundant variant, p21V1, also exceeded that in other death cause groups. Cytoplasmic localization of p21 protein in vascular smooth muscle cells together with substantially increased expression of cardioprotective Pim‐1 especially in chronic hypoxia, but in acute ischemia and hypothermia as well, indicate change of p21 function from cell cycle arrest to promotion of proliferation and cell survival in these cases. In chronic hypoxia deaths the expression of variant p21 alt‐a was highly pronounced whereas the expression of variant p21B was low. In chronic hypoxia deaths the expression of p53 was substantially higher compared to the other groups, being a potential regulator of p21 alt‐a expression. In acute ischemia deaths increased expression of variant p21B, suggested to be proapoptotic in several cell lines, was observed. Our results suggest a role for variant p21 alt‐a in hypoxia and for variant p21B in acute myocardial ischemia. The known cardioprotective aspect of hypothermia might come from an increased p21 protein level. J. Cell. Biochem. 113: 544–552, 2012. © 2011 Wiley Periodicals, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.23377