Homocysteine oxidation and apoptosis: a potential cause of cleft palate.

In Vitro Cell Dev Biol Anim 2003 Jan-Feb;39(1-2):98-105

Division of Child Dental Health, Dental School, University of Bristol, United Kingdom BS1 2LY.

Cleft palate is the most common craniofacial anomaly. Affected individuals require extensive medical and psychosocial support. Although cleft palate has a complex and poorly understood etiology, low maternal folate is known to be a risk factor for craniofacial anomalies. Folate deficiency results in elevated homocysteine levels, which may disturb palatogenesis by several mechanisms, including oxidative stress and perturbation of matrix metabolism. We examined the effect of homocysteine-induced oxidative stress on human embryonic palatal mesenchyme (HEPM) cells and demonstrated that biologically relevant levels of homocysteine (20-100 microM) with copper (10 microM) resulted in dose-dependent apoptosis, which was prevented by addition of catalase but not superoxide dismutase. Incubation of murine palates in organ culture with homocysteine (100 micro) and CuSO(4) (10 microM) resulted in a decrease in palate fusion, which was not significant. Gelatin gel zymograms of HEPM cell-conditioned media and extracts of cultured murine palates, however, showed no change in the expression or activation of pro-matrix metalloproteinase-2 with homocysteine (20 microM-1 mM) with or without CuSO(4) (10 microM). We have demonstrated that biologically relevant levels of homocysteine in combination with copper can result in apoptosis as a result of oxidative stress; therefore, homocysteine has the potential to disrupt normal palate development.

Download full-text PDF

Source
http://dx.doi.org/10.1290/1543-706x(2003)039<0098:hoaaap>2.0.co;2DOI Listing
August 2004
3 Reads

Publication Analysis

Top Keywords

cleft palate
12
oxidative stress
12
relevant levels
8
biologically relevant
8
levels homocysteine
8
cuso4 microm
8
murine palates
8
demonstrated biologically
8
homocysteine
7
palate
5
catalase superoxide
4
addition catalase
4
prevented addition
4
dose-dependent apoptosis
4
apoptosis prevented
4
superoxide dismutase
4
dismutase incubation
4
homocysteine 100
4
100 micro
4
micro cuso4
4

References

(Supplied by CrossRef)

Al-Obdaidi et al.
Arch. Toxicol 1995

Antunes et al.
Biochem. J 2001

Austin et al.
J. Biol. Chem 1998

Bescond et al.
Biochem. Biophys. Res. Commun 1999

Bessede et al.
FASEB J 2001

Blavier et al.
Mol. Biol. Cell 2001

Brenneisen et al.
Free Radic. Biol. Med 1997

Brown et al.
J. Dent. Res 2002

Burgoon et al.
Teratology 2002

Cartwright et al.
Am. J. Clin. Nutr 1964

Chen et al.
Alcohol Clin. Exp. Res 1996

Similar Publications