Placental alkaline phosphatase, insulin, and adenine nucleotides or adenosine synergistically promote long-term survival of serum-starved mouse embryo and human fetus fibroblasts.
Earlier we showed that in serum-starved fibroblasts placental alkaline phosphatase (PALP) can exert growth factor-like effects. Here we report that in mouse embryo (NIH 3T3) and human fetus (HTB-157) fibroblasts, PALP (200 nM) alone provided full protection against serum starvation-induced cell death for 5 days. After 12 days, substantial effects of PALP on cell survival required the copresence of insulin (500 nM) and ATP or adenosine (100 microM). In serum-starved NIH 3T3 cells, PALP induced activating phosphorylation of p42/p44 mitogen-activated protein (MAP) kinases; insulin, but not ATP, had small additional effects. PALP also stimulated the expression of various cyclins; ATP both prolonged and enhanced PALP-induced expression of cyclins A and E. Finally, ATP/adenosine enhanced activation of Akt kinase by insulin. The results suggest that PALP may be a regulator of growth and remodeling of fetal tissues during the second and third trimester of pregnancy when it is expressed.
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The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Mukherjee
J J
JJ
Chung
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T
Kiss
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D016475:3T3 Cells; D000227:Adenine Nucleotides / Q000378:metabolism / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000469:Alkaline Phosphatase; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D016213:Cyclins / Q000096:biosynthesis; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology; D058851:GPI-Linked Proteins; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D013997:Time Factors
D000227:Adenine Nucleotides; D016895:Culture Media, Serum-Free; D016213:Cyclins; D058851:GPI-Linked Proteins; D007328:Insulin; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D000255:Adenosine Triphosphate; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental; D000241:Adenosine