Role of Vitamin C in Chronic Wound Healing
Qi Chen, Margreet C.M. Vissers in Vitamin C, 2020
Cell culture studies demonstrate that vitamin C can promote the differentiation of keratinocytes, which is critical for reepithelialization in wound healing [93]. In an organotypic culture model, vitamin C enhanced differentiation of rat epidermal keratinocytes, increasing filaggrin expression, a differentiation marker, and the number of keratohyalin granules [94]. It also improved the ultrastructural organization of the stratum corneum, enhancing the characteristic basket-weave pattern of this layer, and promoting extracellular lipid deposition. Finally, vitamin C markedly increased the barrier function of the epidermis, as demonstrated by reductions in transepidermal water loss and permeation rates of corticosterone and mannitol. In support of these findings, others have also shown that vitamin C promotes the synthesis and organization of barrier lipids, increases cornified envelope formation during differentiation, and promotes barrier function [95–99]. More specifically, vitamin C has been shown to enhance ceramide synthesis, which is the major lipid component of the stratum corneum [95,97,99]. It particularly increases formation of ceramides 6 and 7 [95], which are hydroxylated derivatives. The increased synthesis seems to be related to upregulation of ceramide synthetic enzymes including serine palmitoyltransferase and ceramide synthase [97,99].
Endotoxic Shock and the Sphingomyelin Pathway
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
Ceramide may also be generated from anabolic reactions. De novo synthesis of ceramide involves the condensation of serine and palmitoyl-CoA to form ketosphinganine (22). The latter is reduced to dihydrosphingosine, acylated to dihydroceramide by the enzyme ceramide synthase, and finally oxidized to ceramide by dihydroceramide reductase. Treatment of P388 and U937 cells with the chemotherapeutic agent daunorubicin results in elevated levels of ceramide (23). Ceramide elevation in this instance did not result from activation of a sphingomyelinase but rather from stimulation of ceramide synthase. The fungal toxin fumonisin Bl, a specific inhibitor of ceramide synthase, was shown to block both daunorubicin-induced cer-amide generation and apoptosis, suggesting that cer-amide synthase activation was obligatory for the death response.
Lipids and Lipid-Like Compounds of Fusarium
Rajendra Prasad, Mahmoud A. Ghannoum in Lipids of Pathogenic Fungi, 2017
Sphingolipid biosynthesis de novo proceeds via the reactions shown in Figure 4.46 In the first and committed step, serine is condensed with palmitoyl-CoA by serine palmitoyltransferase, a pyridoxal 5’-phosphate-dependent enzyme and the resulting 3-keto-sphinganine is reduced to sphinganine using NADPH. Sphinganine is acylated to dihydroceramide (also called N-acyl-sphinganine) by ceramide synthase using various long-chain fatty acyl-CoAs. Head groups (e.g., phosphorylcholine, glucose, galactose, and hundreds of more complex polysaccharides) are subsequently added to the 1-hydroxyl group in various intracellular compartments. It is not clear when the 4,5-inww-double bond of the sphingosine backbone is added, except that it is after acylation of the amino group, and that free sphingosine is not an intermediate of de novo sphingolipid biosynthesis (Figure 4). Sphingolipid turnover is thought to involve the hydrolysis of complex sphingolipids to ceramides and then to sphingosine. Sphingosine is either reacylated or phosphorylated and cleaved to a fatty aldehyde and ethanolamine phosphate, which is incorporated into phosphatidyl ethanolamine. For reviews of sphingolipid metabolism, see references.47-50
Validation of urinary sphingolipid metabolites as biomarker of effect for fumonisins exposure in Kenyan children
Published in Biomarkers, 2019
Ruth Nabwire Wangia, David Peter Githanga, Kathy Siyu Xue, Lili Tang, Omu Aggrey Anzala, Jia-Sheng Wang
The mechanism of FB1 toxicity is attributed to its structural similarity to sphingoid bases, which consists of twenty-carbon backbone as shown in Figure 1 (Wang et al.1991). Due to its structural similarity to sphingoid bases, fumonisin B1 acts as a competitive inhibitor of ceramide synthase (Marasas et al. 2004, Riley et al.2012). The de novo pathway of sphingolipid synthesis is highly dependent on the action of ceramide synthase. The process begins with the condensation of serine and palmitoyl-CoA. This condensation is catalyzed by serine palmitoyl transferase to generate 3-ketodihydrosphingosine which is subsequently reduced to sphinganine (Sa). Sa is then N-acylated by ceramide synthase to produce dihydroceramide (dhc) that through the action of dhc-desaturase is reduced to ceramide. In the presence of fumonisin exposure, FB1 inhibits the N-acylation process by blocking ceramide synthase (Turner et al.1999, Voss et al.2002, 2006, Zitomer et al.2009). Ultimately, this inhibition results in accumulation of intracellular Sa that can eventually lead to oxidatively generated DNA damage, sphingomyelin depletion and altered function of sphingolipids as second messengers
Radiation-induced neuropathological changes in the oligodendrocyte lineage with relevant clinical manifestations and therapeutic strategies
Published in International Journal of Radiation Biology, 2022
Additionally, ceramide and protein kinase B (PKB)/Akt were found to also be implicated in radiation-induced apoptosis of oligodendrocytes. Irradiated primary cultures of neonatal rat oligodendrocytes exhibited a dose-dependent downregulation of PKB activity. This decrease occurred prior to the onset of oligodendroglial apoptosis, suggesting that the PKB/Akt pathway may be implicated in radiation-induced apoptosis. The irradiated cells also had increased ceramide levels that preceded the onset of apoptosis 4 hours after a single dose of 10 Gy (Lu and Wong 2004). Endogenous ceramide can be generated via the activation of acid sphingomyelinase (ASMase) and subsequent hydrolysis of sphingomyelin, as well as de novo synthesis by ceramide synthase. Both pathways were shown to be required for radiation-induced apoptosis in B lymphocytes and lymphoblast’s (Vit and Rosselli 2003). However, inhibition of ASMase and ceramide synthase activities did not alter the apoptotic response of irradiated oligodendrocytes (Lu and Wong 2004). A recent study in irradiated Jurkat T cells revealed that a single dose of 10 Gy physically disrupted lysosomal membrane integrity, which led to the release of ASMase and subsequent increase in ceramide levels as well as cellular apoptosis (Ferranti et al. 2020). Hence, it is possible that similar mechanisms may also be involved in radiation-induced apoptosis of oligodendrocytes which warrant further investigations.
Fermented dried Citrus unshiu peel extracts exert anti-inflammatory activities in LPS-induced RAW264.7 macrophages and improve skin moisturizing efficacy in immortalized human HaCaT keratinocytes
Published in Pharmaceutical Biology, 2019
Chulwon Kim, Jun Ji, Seung Ho Baek, Jong Hyun Lee, In Jin Ha, Soon Sung Lim, Hong Jae Yoon, Yun Je Nam, Kwang Seok Ahn
Ceramides are a type of sphingolipid and consist of a sphingoid base and a saturated fatty acid moiety. Ceramides are present as a dominant lipid in the stratum corneum (SC), the most upper layer of the epidermis of the skin and play a crucial role in its water-holding and barrier function (Takeda et al. 2018). Until recently, more than 12 types of ceramide have been designated in human SC (Masukawa et al. 2008). Ceramides in the epidermis are synthesized by several enzymes such as serine palmitoyltransferase (SPT) (Hanada 2003), ceramide synthase (CerS) (Levy and Futerman 2010), glucosylceramide synthase (GCS) (Hamanaka et al. 2002), β-glucocerebrosidese (GBA) (Takagi et al. 1999), sphingomyelin synthase (SMS) (Tafesse et al. 2006), and acid sphingomyelinase (ASM) (Jenkins et al. 2009). SPT and CerS are involved in the de novo synthesis of ceramides. SPT catalyses the condensation of serine and palmitoyl-CoA as the first step of de novo synthesis. The term `Filaggrin' (derived from `filament-aggregating protein') was first coined in 1981 to describe a class of structural protein that had been isolated from the stratum corneum (Steinert et al. 1981). By aggregating keratin filaments into keratin fibrils within the cytoskeleton of corneocytes, filaggrin is responsible for the mechanical strength and integrity of the stratum corneum (O'Regan et al. 2008). Filaggrin has also been designated as a natural moisturizing factor protein that contributes to the permeable barrier as an aggregated particle comprised of profilaggrin (Kezic et al. 2009).
Related Knowledge Centers
- Catalysis
- Ceramide
- Chemical Reaction
- Coenzyme A
- Enzyme
- Integral Membrane Protein
- Sphingosine
- Substrate
- Acyl-Coa
- Product