Menaquinone-4 Concentration Is Correlated with Sphingolipid Concentrations in Rat Brain

Abstract

Studies with animals support a role for vitamin K (VK) in the biosynthesis of sphingolipids, a class of complex lipids present in high concentrations in the brain. In mice and rats, VK deficiency decreases levels of brain sulfatides and causes behavioral alterations. In light of its heterogeneity and to better understand the role of VK in the brain, we characterized the distribution of the two main VK vitamers, phylloquinone (K1) and menaquinone-4 (MK-4), in nine distinct brain regions. Weaning female Sprague-Dawley rats (n=5/dietary group) were fed diets containing either low (L, 80 microg/kg diet), adequate (A, 500 microg/kg diet) or high (H, 2000 microg/kg diet) levels of K1 for 6 mo. The main form of VK in the brain was MK-4, and it was present in significantly higher concentrations in myelinated regions (the pons medulla and midbrain) than in nonmyelinated regions. Both regional K1 and MK-4 increased with K1 intake (P<0.05). Sphingolipid distribution varied across brain regions (P<0.001) but was not affected by K1 intake. In the L and A groups but not the H group, brain MK-4 concentration was positively correlated with the concentrations of sulfatides (L, r=0.518; A, r=0.479) and sphingomyelin (L, r=0.515; A, r=0.426), and negatively correlated with ganglioside concentration (L, r=-0.398); A, r=-0.353). Sphingolipids are involved in major cellular events such as cell proliferation, differentiation and survival. The strong associations reported here between brain MK-4 and sphingomyelin, sulfatides and gangliosides suggest that this vitamer may play an important role in the brain.

Vitamin K Metabolism in a Rat Model of Chronic Kidney Disease

“…2). The low vitamin K1 dose was chosen to create a mild deficiency state while maintaining coagulation [31,32] . The high vitamin K1 dose was selected based on previous work demonstrating that this dose of K1 regressed warfarin-induced medial calcification in a non-CKD model, and our own work that demonstrated this dose was also sufficient to regress CKD-induced vascular calcification [8,33,34] .…”

Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification

“…As reduced vitamin K 1 and reduced MK4 are both cofactors in the γ-carboxylation system, this finding has raised questions about additional effects of MK4 in the arterial wall which may enhance inhibition of arterial calcification. MK4 has been shown to effect gene expression of osteoblastic bone markers by binding to the steroid and xenobiotic receptor (SXR) [17]. This observation triggered our curiosity to find out if MK4 could affect gene expression in VSMCs which could result in altered concentrations of known calcification inhibitory proteins in the vessel wall to levels that would enhance inhibition of calcification.…”

Effects of Vitamin K1 Supplementation on the Risk Factors to the Stroke and on Memory in Spontaneously Hypertensive Rats Stroke Prone (SHR-sp)

“…Regarding to the effects of phylloquinone supplementation on the neurological response, the sensory-motor tests revealed no statistical difference between the treated and control groups in the present assay; however memory functioning was significantly improved by this vitamin. Carrié et al (2004), also suggested that vitamin K1 has a crucial role on memory function in young rats, which was attributed to it action on sphingolipids metabolism. According to those authors, vitamin K supplementation promoted a decrease of ceramide brain levels in the hippocampal region.…”

“…According to those authors, vitamin K supplementation promoted a decrease of ceramide brain levels in the hippocampal region. Data from in vivo and in vitro studies suggest that the role of vitamin K is in the regulation of many enzymes involved in the metabolism of sphingolipids in myelin-rich regions of the brain (Denisova and Booth 2005), mainly in the medulla, pons, and midbrain, where there are higher concentration of this vitamin (Carrié et al 2004). It has been shown that ceramides act in processes of cellular growth, division, differentiation and apoptosis (Zeidan and Hannun 2007), but, when present in high concentrations, are strongly related to the inflammatory processes (Ballou et al 1996) and to the generation of reactive oxygen species by mitochondria (Jana et al 2009).…”