Abstract
A tight control of proliferation and cell death is required to maintain homeostasis in multicellular organisms. Several specific pro- and anti-apoptotic regulators and pathways have been deciphered being responsible for these complex tasks. Here we describe a human serum-borne activity promoting cellular fitness and inhibiting apoptosis after a plethora of different cell death stimuli. The factor(s) do not inhibit a specific death pathway, instead it/they can be considered as general pro-survival factor(s) for cultured cells. The activity is heat stable (30 min, 96°C), co-migrates with albumin in size exclusion chromatography, and is sensitive to chemical delipidation. A similar activity is observed in native, non-delipidated preparations of human albumin, while delipidated albumin is not effective. These properties point to heat stable factors that exert anti-apoptotic activities, most likely albumin bound bioactive lipids. The activity prevented Akt dephosphorylation and degradation, after apoptosis induction by staurosporine and the production of reactive oxygen species after UV-B irradiation. In conclusion human serum-enriched bioactive lipids promote survival of cultured cells overriding the pro-apoptotic effects of a variety of apoptosis inducing agents.
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Acknowledgements
This work was supported by “Deutsche Forschungsgemeinschaft” SFB 643 (project B5), by the Interdisciplinary Centre for Clinical Research (IZKF) (project number A4 and N2) at the University Hospital of the University of Erlangen-Nuremberg, by the University of Erlangen’s ELAN program, S. F. was supported by the DFG research training grant GK592 and the University of Erlangen’s ELAN program. M. S. and HM. L. were supported by DFG research grant (project Lo437/5-3).
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Schiller, M., Franz, S., Heyder, P. et al. Hypothesis: human serum-borne albumin bound lipids promote cellular survival after apoptosis induction by a variety of stimuli. Apoptosis 13, 319–328 (2008). https://doi.org/10.1007/s10495-007-0168-3
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DOI: https://doi.org/10.1007/s10495-007-0168-3