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The Potential of Microbial Mediated Fermentation Products of Herbal Material in Anti-Aging Cosmetics
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Type III collagen comprises approximately 20% of the total collagen in the skin, concentrated in the mesh-like papillary dermis, while the remaining 80% is comprised of type-I collagen, concentrated in the reticular dermis. Structurally, type III collagen is a homotrimer of α1(III) chains and type I, a heterotrimer of two α1(I) chains and one α2(I) chain arranged in an anti-parallel conformation to produce more dense fibers (Cole et al., 2018). These fibers are enzymatically cross linked following the secretion of procollagen and its maturation to confer resistance to proteolytic cleavage. The proteolytic removal of C and N terminal pro-peptides facilitates the maturation of procollagen into mature collagen fibers. For instance, in type-I collagen various intracellular lysine residues containing α1(I) and α2(I) chains are converted to hydroxylysine through the action of lysyl hydroxylase, while extracellular lysine and hydroxylysine residues are converted to aldehydes through the action of lysyl oxidase. This process enables spontaneous, non-reducible inter- and intra-peptide crosslinking. The action of lysyl oxidase is crucial in facilitating matrix deposition of elastin fibers and prevention of excessive elasticity (Cole et al., 2018).
Future Therapy of Interstitial Lung Diseases
Published in Lourdes R. Laraya-Cuasay, Walter T. Hughes, Interstitial Lung Diseases in Children, 2019
One of the first processing steps required in collagen biosynthesis is the hydroxylation of prolyl and lysyl residues by the enzymes prolyl and lysyl hydroxylase. Hydroxylation is a critical step in collagen biosynthesis because unhydroxylated collagen cannot assume a helical conformation at physiological temperatures. The disease scurvy is a well-recognized example of lack of procollagen hydroxylation caused by dietary deficiency of ascorbic acid, an essential cofactor for prolyl hydroxylase. Analogues have been developed which inhibit prolyl hydroxylase,16 but it is not known whether these agents act in vivo.
Treatment of skin with antioxidants
Published in Roger L. McMullen, Antioxidants and the Skin, 2018
Ascorbic acid, or vitamin C, is the major water-soluble antioxidant in skin and most other body tissues. It is likewise found in a variety of fruits and vegetables (Figure 8.3) and is often obtained via diet or through vitamin supplements. Vitamin C is integral in managing the free radical levels in the aqueous and interfacial zones of skin. It is also key to vitamin E activity, as it recycles the oxidized form of alpha-tocopherol back to its active form (Chapter 3). In addition, vitamin C is a cofactor important for the synthesis of collagen and maintenance of sustainable MMP levels.12,39,40 It specifically acts as a cofactor for prolyl hydroxylase and lysyl hydroxylase in the synthesis of collagen (Chapter 3). A lack of dietary vitamin C results in the degenerative disease scurvy, which was especially prevalent among European sailors between the sixteenth and nineteenth centuries.41 In recent years, ascorbic acid derivatives have been used as skin whitening agents, whereby they act as inhibitors of tyrosinase activity, thereby impeding melanin synthesis.42
Functional role of ascorbic acid in the central nervous system: a focus on neurogenic and synaptogenic processes
Published in Nutritional Neuroscience, 2022
Morgana Moretti, Ana Lúcia S. Rodrigues
Ascorbic acid (vitamin C) is a water-soluble vitamin that exerts numerous essential cellular and molecular functions, including neuronal neuromodulation and regulation of CNS homeostasis [1]. Ascorbic acid is a reducing agent, and several physiological functions of this compound depend on its redox property [2]. Aside from its antioxidant effects [3] and its ability to act as a cofactor for the collagen biosynthesis enzymes lysyl hydroxylase and prolyl hydroxylase [4], ascorbate (the dominant form at physiological pH) is required as a cofactor for several enzymes that play an important role in the central nervous system. For example, it is a cofactor of dopamine β-hydroxylase, the enzyme that catalyzes the conversion of dopamine into norepinephrine [5]. Ascorbate is also an essential cofactor for the synthesis of many neuropeptides [6]. Moreover, it is involved in the formation of the myelin sheath by Schwann cells [7,8], and regulates the sodium-potassium ATPase enzyme [9,10]. Studies also demonstrated that ascorbate can modulate acetylcholine release in synaptic vesicles from rat brain synaptosomes [11] and cultured adrenal chromaffin cells [12].
Renal fibrosis as a hallmark of diabetic kidney disease: potential role of targeting transforming growth factor-beta (TGF-β) and related molecules
Published in Expert Opinion on Therapeutic Targets, 2022
Jiali Tang, Fang Liu, Mark E. Cooper, Zhonglin Chai
Besides the activity of TGF-β in promoting overexpression of ECM as discussed above, TGF-β is able to reduce the degradation of ECM [86]. It not only reduces the expression of MMPs/collagenases but also promotes the expression of TIMPs (inhibitor of the ECM-degrading MMPs), thereby contributing to the reduction in ECM degradation [86–89]. Moreover, TGF-β1 expression facilitates the formation of plasminogen activator inhibitor-1 (PAI-1), which significantly inhibits ECM degradation contributing to renal fibrosis [90,91]. On the other hand, cross-linking among ECM fibers can increase the resistance of ECM to proteolytic degradation by MMPs [92]. TGF-β1 has been proven to upregulate the level of lysyl oxidases, promoting formation of abnormal matrix cross-linking between collagen and elastin fibers [93,94]. In addition, TGF-β1 also induces the expression of procollagen lysyl hydroxylase 2, which results in more stable collagen cross-linking[95].
Glimpses into the molecular pathogenesis of Peyronie’s disease
Published in The Aging Male, 2020
Evert-Jan P. M. ten Dam, Mels F. van Driel, Igle Jan de Jong, Paul M. N. Werker, Ruud A. Bank
Collagen synthesis is a complex process, and many enzymes are involved. Chaperones assist in folding of the procollagen molecules and propeptidases cleave off the propeptides to convert procollagen into collagen. Conversion of proline into 3-hydroxyproline or 4-hydroxyproline is catalyzed by prolyl hydroxylases, conversion of lysine (Lys) into 4-hydroxylysine (Hyl) by lysyl hydroxylases, and cross-linking is initiated by lysyl oxidases [47]. We used a low-density array (Table 2 andFigure 3) to quantify the expression of these enzymes, to clarify whether there were possible aberrations in (pro)collagen processing. An important post-translational modification of collagen is the conversion of triple helical lysine (Lys) into hydroxylysine (Hyl), and the addition of sugars to Hyl, resulting in the glycosylated residues galactosylhydroxylysine (Gal–Hyl) and glucosylgalactosylhydroxylysine (Glc–Gal–Hyl) [26]. It has now been established that the conversion of triple helical Lys into Hyl is catalyzed by lysyl hydroxylase 1 (encoded by PLOD1) and lysyl hydroxylase 3 (encoded by PLOD3), and that the formation of Glc–Gal–Hyl (but not Gal-Hyl) is catalyzed by lysyl hydroxylase 3 [26]. We have observed no differences in mRNA levels of PLOD1 between plaque and control tissue, but there was a major increase in mRNA levels of PLOD3 in plaque tissue. Therefore, an overhydroxylation of Lys in PD tissue is expected, as well as increased levels of Glc–Gal–Hyl. A Lys overhydroxylation and a Hyl overglycosylation have been reported for affected DD tissues [37,40,41].