The effect of active serum albumin on PC12 cells

I. Neurite retraction and activation of the phosphoinositide second messenger system

David Dyer, Gabor Tigyi, Ricardo Miledi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Vertebrate blood sera contain a factor that triggers oscillatory chloride currents in Xenopus oocytes through activation of the phosphoinositide/Ca2+ second messenger system. The active serum component consists of lipids bound to an isoform of serum albumin that we have named active serum albumin (ASA). In undifferentiated PC12 cells, micromolar concentrations of ASA inhibit the early morphological changes induced by NGF, whereas in differentiated PC12 cells ASA caused a rapid withdrawal of neurites, which was reversible and dependent upon culture age. In contrast to normal serum, plasma and thrombin did not cause neurite retraction. Preincubation of ASA with monospecific antibodies to serum albumin suppressed its ability to induce neurite retraction in a dose dependent fashion. As in the oocyte, ASA activated the phosphatidylinositol second messenger system of PC12 cells, causing a several fold increase in Ins1,4,5P3 levels within minutes of application. The Ins1,4,5P3 increase was also blocked, in a titratable fashion, when ASA was preincubated with monospecific antibodies to serum albumin. This suggests that ASA-induced neurite retraction in PC12 cells may depend, at least in part, on activation of the phosphatidylinositol second messenger system. Results involving albumin-depleted sera show that ASA is the main factor responsible for serum vulnerability of neurites in PC12 cells. These findings point to some limitations in the use of serum in culture media, and raise the possibility that the serum factor may impair neuronal plasticity in disorders that are accompanied by the activation of blood coagulation together with a breakdown of the blood-brain barrier.

Original languageEnglish (US)
Pages (from-to)293-301
Number of pages9
JournalMolecular Brain Research
Volume14
Issue number4
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

PC12 Cells
Second Messenger Systems
Neurites
Phosphatidylinositols
Serum Albumin
Serum
Oocytes
Neuronal Plasticity
Antibodies
Blood Coagulation
Nerve Growth Factor
Xenopus
Blood-Brain Barrier
Thrombin
Culture Media
Vertebrates
Chlorides
Protein Isoforms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

The effect of active serum albumin on PC12 cells : I. Neurite retraction and activation of the phosphoinositide second messenger system. / Dyer, David; Tigyi, Gabor; Miledi, Ricardo.

In: Molecular Brain Research, Vol. 14, No. 4, 01.01.1992, p. 293-301.

Research output: Contribution to journalArticle

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