Hypothesis: human serum-borne albumin bound lipids promote cellular survival after apoptosis induction by a variety of stimuli.
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 degrees 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.
Schiller
Martin
M
Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. martin.schiller@med.uni-heidelberg.de
Franz
Sandra
S
Heyder
Petra
P
Voll
Reinhard E
RE
Gaipl
Udo S
US
Lorenz
Hanns-Martin
HM
Kalden
Joachim R
JR
Herrmann
Martin
M
D017209:Apoptosis; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology*; D008055:Lipids / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D018384:Oxidative Stress; D044967:Serum / Q000502:physiology; D012709:Serum Albumin / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008055:Lipids; D012709:Serum Albumin; D051058:Oncogene Protein v-akt; D019311:Staurosporine