Elevated Expression of Liver γ-Cystathionase Is Required for the Maintenance of Lactation in Rats

Abstract

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.

The Inhibitory Effects of Hydrogen Sulfide on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

“…Two classes of pyridoxal-5'-phosphate-dependent enzymes, CBS and CSE are responsible for the majority of the endogenous production of H2S in mammalian tissues that use L-cysteine as the main substrate [19,20]. CSE is expressed in a range of mammalian cells and tissues, and it seems to be the main H2S-forming enzyme in the liver, kidney, and cardiovascular system and, CBS is mainly expressed in the liver and central nervous system [8,21]. Florucci et al (2006) have reported expression of CSE mainly in the liver, vascular and nonvascular smooth muscle but, a low level of expression of the CSE transcript, protein, and enzymatic activity is also detectable in the small intestine and stomach of rodents [22].…”

Cystathionine γ-Lyase Overexpression Inhibits Cell Proliferation via a H2S-dependent Modulation of ERK1/2 Phosphorylation and p21Cip/WAK-1

“…It also uses L-cysteine as an alternative substrate to form H 2 S (4). As a pyridoxal phosphate-dependent enzyme, CSE is expressed in a range of mammalian cells and tissues, and it seems to be the main H 2 S-forming enzyme in the liver, kidney, and cardiovascular system (7,8). Deficiency of H 2 S-producing enzymes results in some disorders such as homocystinuria, which are characterized by mental retardation, skeletal abnormalities, increased urine homocysteine, increased risks of thromboembolism, and early onset of atherosclerosis (9,25,26).…”

“…Two pyridoxal-5Ј-phosphate-dependent enzymes, cystathionine ␤-synthase (EC 4.2.1.22) and cystathionine ␥-lyase (CSE) 1 (EC 4.4.1.1), are responsible for the endogenous production of H 2 S in mammalian tissues, which use L-cysteine as the main substrate (3)(4)(5). Cystathionine ␤-synthase is a predominant H 2 S-generating enzyme in the brain and nervous system (6), and CSE is mainly expressed in liver, kidney, and vascular smooth muscles (7,8). Cystathionine ␤-synthase and CSE are important for the metabolism of sulfur-containing amino acids (e.g.…”

Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure

“…CBS is a predominant H 2 S-generating enzyme in the brain and nervous tissues (1,12), and CSE is mainly expressed in the liver, kidney, and vascular smooth muscle cells (3,61). Although Hcy has been shown to promote CSE activity at its lower Fig.…”