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University of College London; Specific protein kinase C isoforms augment neural tube defect prevention

Posted on: Thursday, 12 February 2004, 06:00 CST

2004 FEB 18 - (NewsRx.com & NewsRx.net) -- Specific protein kinase C isoforms augment neural tube defect prevention.

According to a study from England, "a proportion of neural tube defects (NTDs) can be prevented by maternal folic acid supplementation, although some cases are unresponsive. The curly tail mutant mouse provides a model of folate-resistant NTDs, in which defects can be prevented by inositol therapy in early pregnancy. Hence, inositol represents a possible novel adjunct therapy to prevent human NTDs."

"The present study investigated the molecular mechanism by which inositol prevents mouse NTDs. Activation of protein kinase C (PKC) is known to be essential, and we examined neurulation-stage embryos for PKC expression and applied PKC inhibitors to curly tail embryos developing in culture. Although all known PKC isoforms were detected in the closing neural tube, use of chemical PKC inhibitors identified a particular requirement for 'conventional' PKC isoforms," explained P. Cogram and colleagues, University College London, Institute of Child Health.

"Peptide inhibitors offer selective inhibition of individual PKCs, and we demonstrated isoform-specific inhibition of PKC in embryonic cell cultures. Application of peptide inhibitors to neurulation-stage embryos revealed an absolute dependence on the activity of PKCbetaI and gamma for prevention of NTDs by inositol, and partial dependence on PKCzeta, whereas other PKCs (alpha, betaII delta, and epsilon) were dispensable."

"To investigate the cellular action of inositol and PKCs in NTD prevention, we examined cell proliferation in curly tail embryos. Defective proliferation of hindgut cells is a key component of the pathogenic sequence leading to NTDs in curly tail. Hindgut cell proliferation was stimulated specifically by inositol, an effect that required activation of PKCbetaI," scientists indicated.

"Our findings reveal an essential role of specific PKC isoforms in mediating the prevention of mouse NTDs by inositol," Cogram's team said.

Cogram and colleagues published the results of their research in Human Molecular Genetics (Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol. Hum Mol Genet, 2004;13(1):7-14).

For additional information, contact A.J. Copp, University College London, Institute Child Hlth, Neural Development Unit, 30 Guilford St., London WC1N 1EH, UK.

The publisher of the journal Human Molecular Genetics can be contacted at: Oxford University Press, Great Clarendon St., Oxford OX2 6DP, UK.

The information in this article comes under the major subject areas of Enzymology, Neuroscience, Obstetrics and Cell Biology.

This article was prepared by Biotech Week editors from staff and other reports. Copyright 2004, Biotech Week via NewsRx.com & NewsRx.net.

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