Protective effect of transforming growth factor-β1 on β-amyloid neurotoxicity in rat hippocampal neurons

Jochen H M Prehn, Vytautas P. Bindokas, Joaquín Jordán, María F. Galindo, Ghanashyam D. Ghadge, Raymond P. Roos, Lawrence H. Boise, Craig B. Thompson, Stanislaw Krajewski, John C. Reed, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

152 Scopus citations


Neurodegeneration associated with Alzheimer's disease is believed to involve toxicity to β-amyloid (Aβ) and related peptides. Treatment of cultured rat hippocampal neurons with Aβ 1-40 (1 μM) or the active fragment Aβ 25-35 (1 μM) for 5 days led to a ~40-50% decrease in neuronal viability. The hydrophilic anti-oxidant ascorbic acid (300 μM) and the lipophilic antioxidant 2-mercaptoethanol (10 μM) both protected significantly against Aβ neurotoxicity. Despite the protective effects of these anti-oxidants, both acute and chronic treatments with Aβ 25-35 did not increase production of superoxide anions, as monitored with the fluorescent probe hydroethidine. Similarly, overexpression of Cu/Zn-superoxide dismutase using adenovirus-mediated gene transfer did not protect against Aβ neurotoxicity. Aβ neurotoxicity, however, was prevented in cultures infected with a recombinant, replication-defective adenovirus overexpressing the Ca2+ binding protein calbindin D(28k). Transforming growth factor-β1 (TGF- β1) has been shown to protect neurons against both Ca2+- and free radical- mediated neuronal degeneration. We found that Aβ neurotoxicity was significantly attenuated by single treatments with TGF-β1 (0.1-10 ng/ml) and prevented by repetitive treatments (10 ng/ml/day). The protective effects of TGF-β1 were associated with a preservation of mitochondrial potential and function, as determined with rhodamine-123-based microfluorimetry. Because both increased oxidative stress and pathophysiological Ca2+ fluxes can impair mitochondrial function, preservation of mitochondrial potential by TGF-β1 could be directly associated with its protection against Aβ neurotoxicity. The ability of TGF-β1 to increase the expression of the anti- apoptotic proteins Bcl-2 and Bcl-x(L) is discussed in this context.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
JournalMolecular Pharmacology
Issue number2
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Protective effect of transforming growth factor-β1 on β-amyloid neurotoxicity in rat hippocampal neurons'. Together they form a unique fingerprint.

  • Cite this

    Prehn, J. H. M., Bindokas, V. P., Jordán, J., Galindo, M. F., Ghadge, G. D., Roos, R. P., Boise, L. H., Thompson, C. B., Krajewski, S., Reed, J. C., & Miller, R. J. (1996). Protective effect of transforming growth factor-β1 on β-amyloid neurotoxicity in rat hippocampal neurons. Molecular Pharmacology, 49(2), 319-328.