Differentiation of PC12 cells with nerve growth factor is associated with induction of transin synthesis and release

H. L. Fillmore, C. L. Mainardi, Karen Hasty

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Abstract

We have identified and characterized a calcium‐dependent metalloproteinase which is induced in rat pheochromocytoma cells (PC12 cells) during differentiation with nerve growth factor (NGF). Assays of proteolytic activity in media from differentiated PC 12 cell cultures revealed a NGF‐dependent increase in the activity of a proteinase which has a molecular weight of 62 kDa. Studies using serine, thiol, and metalloproteinase inhibitors demonstrated that the secreted enzyme is a metalloproteinase. Treatment of culture supernatants with aminophenylmercuric acid (APMA), a known activator of metalloproteinases, resulted in a decrease in the molecular weight of the proteinase. Western blot analysis of culture media from NGF‐treated PC12 cells using an antibody directed against a synthetic peptide of rat transin identified this metalloproteinase as transin. Treatment of PC12 cells with acidic and basic fibroblast growth factor (FGF) resulted in distinct morphological changes as well as transin release. Incubation with epidermal growth factor (EGF) did not induce transin release. Dexamethasone inhibited the induction of transin release by NGF. 35S‐methionine labeling and immunoprecipitation of newly synthesized proteins from culture supernatants confirmed that NGF induced the synthesis of this enzyme 8 hr after NGF treatment The NGF‐dependent induction of transin, a calcium‐dependent metalloproteinase which degrades type IV collagen, laminin, and fibronectin suggests that transin may function to degrade the surrounding extracellular matrix during the invasive process of axonal elongation in neuronal development thereby allowing the movement of growth cones and axons toward specific targets.

Original languageEnglish (US)
Pages (from-to)662-669
Number of pages8
JournalJournal of Neuroscience Research
Volume31
Issue number4
DOIs
StatePublished - Jan 1 1992

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Matrix Metalloproteinase 3
PC12 Cells
Nerve Growth Factor
Metalloproteases
Peptide Hydrolases
Molecular Weight
Fibroblast Growth Factor 1
Growth Cones
Collagen Type IV
Pheochromocytoma
Laminin
Fibroblast Growth Factor 2
Enzymes
Fibronectins
Immunoprecipitation
Sulfhydryl Compounds
Epidermal Growth Factor
Serine
Dexamethasone
Extracellular Matrix

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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Differentiation of PC12 cells with nerve growth factor is associated with induction of transin synthesis and release. / Fillmore, H. L.; Mainardi, C. L.; Hasty, Karen.

In: Journal of Neuroscience Research, Vol. 31, No. 4, 01.01.1992, p. 662-669.

Research output: Contribution to journalArticle

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