Elevated expression of liver gamma-cystathionase is required for the maintenance of lactation in rats.
Liver gamma-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation. This is reversible by N-acetylcysteine administration. To study the role of liver gamma-cystathionase and the intertissue flux of glutathione during lactation, we used lactating and virgin rats fed liquid diets. Virgin rats were divided into two groups as follows: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats); the other virgin group was fed the normal liquid diet (control). The expression and activity of liver gamma-cystathionase were significantly greater in lactating rats and in high protein diet-fed virgin rats compared with control rats. The total glutathione [reduced glutathione (GSH) + oxidized glutathione (GSSG)] released per gram of liver did not differ in lactating rats or in high protein diet-fed rats, but it was significantly higher in these two groups than in control virgin rats. Liver size and the GSH + GSSG released by total liver were significantly higher in lactating rats than in high protein diet-fed virgin rats, and this difference was similar to the amount of glutathione taken up by the mammary gland (454.2 +/- 36.0 nmol/min). The uptake of total glutathione by the lactating mammary gland was much higher than the uptakes of free L-cysteine and L-cystine, which were negligible. These data suggest that the intertissue flux of glutathione is an important mechanism of L-cysteine delivery to the lactating mammary gland, which lacks gamma-cystathionase activity. This emphasizes the physiologic importance of the increased expression and activity of liver gamma-cystathionase during lactation.
Barber
T
T
Departamento de Bioquímica y Biología Molecular, Facultade de Medicina-Farmacia, Universitat de Valencia, Spain.
Triguero
A
A
Martínez-López
I
I
Torres
L
L
García
C
C
Miralles
V J
VJ
Viña
J R
JR
D000111:Acetylcysteine / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D003553:Cystine / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007774:Lactation / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008321:Mammary Glands, Animal / Q000378:metabolism; D008892:Milk / Q000737:chemistry; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D000480:Alkynes; D000596:Amino Acids; D004044:Dietary Proteins; D004791:Enzyme Inhibitors; D003553:Cystine; C009055:propargylglycine; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D003545:Cysteine; D005998:Glycine; D000111:Acetylcysteine