-
Clinical Interventions in Aging 2006Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the... (Review)
Review
Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy ofretinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confirm their advantage in the delivery of topical retinoids.
Topics: Adapalene; Dermatologic Agents; Dermis; Epidermis; Humans; Naphthalenes; Nicotinic Acids; Retinaldehyde; Retinoids; Skin Aging; Treatment Outcome; Tretinoin; Vitamin A Deficiency
PubMed: 18046911
DOI: 10.2147/ciia.2006.1.4.327 -
Biochimica Et Biophysica Acta May 2014Proteorhodopsins are the most abundant retinal based photoreceptors and their phototrophic function might be relevant in marine ecosystems. Here, we describe their... (Review)
Review
Proteorhodopsins are the most abundant retinal based photoreceptors and their phototrophic function might be relevant in marine ecosystems. Here, we describe their remarkable molecular properties with a special focus on the green absorbing variant. Its distinct features include a high pKa value of the primary proton acceptor stabilized through an interaction with a conserved histidine, a long-range interaction between the cytoplasmic EF loop and the chromophore entailing a particular mode of color tuning and a variable proton pumping vectoriality with complex voltage-dependence. The proteorhodopsin family represents a profound example for structure-function relationships. Especially the development of a biophysical understanding of green proteorhodopsin is an excellent example for the unique opportunities offered by a combined approach of advanced spectroscopic and electrophysiological methods. This article is part of a Special Issue entitled: Retinal Proteins-You can teach an old dog new tricks.
Topics: Amino Acid Sequence; Animals; Histidine; Hydrogen-Ion Concentration; Ion Transport; Light; Models, Molecular; Molecular Sequence Data; Patch-Clamp Techniques; Protein Conformation; Proteobacteria; Protons; Retinaldehyde; Rhodopsin; Rhodopsins, Microbial; Structure-Activity Relationship; Xenopus
PubMed: 24060527
DOI: 10.1016/j.bbabio.2013.09.010 -
Advances in Experimental Medicine and... 2015Colorectal cancer (CRC) and pancreatic cancer are two very significant contributors to cancer-related deaths. Chronic alcohol consumption is an important risk factor for... (Review)
Review
Colorectal cancer (CRC) and pancreatic cancer are two very significant contributors to cancer-related deaths. Chronic alcohol consumption is an important risk factor for these cancers. Ethanol is oxidized primarily by alcohol dehydrogenases to acetaldehyde, an agent capable of initiating tumors by forming adducts with proteins and DNA. Acetaldehyde is metabolized by ALDH2, ALDH1B1, and ALDH1A1 to acetate. Retinoic acid (RA) is required for cellular differentiation and is known to arrest tumor development. RA is synthesized from retinaldehyde by the retinaldehyde dehydrogenases, specifically ALDH1A1, ALDH1A2, ALDH1A3, and ALDH8A1. By eliminating acetaldehyde and generating RA, ALDHs can play a crucial regulatory role in the initiation and progression of cancers. ALDH1 catalytic activity has been used as a biomarker to identify and isolate normal and cancer stem cells; its presence in a tumor is associated with poor prognosis in colon and pancreatic cancer. In summary, these ALDHs are not only biomarkers for CRC and pancreatic cancer but also play important mechanistic role in cancer initiation, progression, and eventual prognosis.
Topics: Acetaldehyde; Aldehyde Dehydrogenase; Cell Proliferation; Colorectal Neoplasms; Humans; Pancreatic Neoplasms; Retinaldehyde; Tretinoin
PubMed: 25427913
DOI: 10.1007/978-3-319-09614-8_16 -
Biochimica Et Biophysica Acta May 2014Channelrhodopsins are microbial-type rhodopsins that function as light-gated cation channels. Understanding how the detailed architecture of the protein governs its... (Review)
Review
Channelrhodopsins are microbial-type rhodopsins that function as light-gated cation channels. Understanding how the detailed architecture of the protein governs its dynamics and specificity for ions is important, because it has the potential to assist in designing site-directed channelrhodopsin mutants for specific neurobiology applications. Here we use bioinformatics methods to derive accurate alignments of channelrhodopsin sequences, assess the sequence conservation patterns and find conserved motifs in channelrhodopsins, and use homology modeling to construct three-dimensional structural models of channelrhodopsins. The analyses reveal that helices C and D of channelrhodopsins contain Cys, Ser, and Thr groups that can engage in both intra- and inter-helical hydrogen bonds. We propose that these polar groups participate in inter-helical hydrogen-bonding clusters important for the protein conformational dynamics and for the local water interactions. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks.
Topics: Amino Acid Sequence; Chlamydomonas reinhardtii; Computational Biology; Hydrogen Bonding; Ion Transport; Light; Models, Molecular; Molecular Sequence Data; Protein Conformation; Proteobacteria; Retinaldehyde; Rhodopsins, Microbial; Sequence Alignment; Structural Homology, Protein; Water
PubMed: 24252597
DOI: 10.1016/j.bbabio.2013.11.005 -
Biomolecules Dec 2019The concentration of all--retinoic acid, the bioactive derivative of vitamin A, is critically important for the optimal performance of numerous physiological processes.... (Review)
Review
The concentration of all--retinoic acid, the bioactive derivative of vitamin A, is critically important for the optimal performance of numerous physiological processes. Either too little or too much of retinoic acid in developing or adult tissues is equally harmful. All--retinoic acid is produced by the irreversible oxidation of all--retinaldehyde. Thus, the concentration of retinaldehyde as the immediate precursor of retinoic acid has to be tightly controlled. However, the enzymes that produce all--retinaldehyde for retinoic acid biosynthesis and the mechanisms responsible for the control of retinaldehyde levels have not yet been fully defined. The goal of this review is to summarize the current state of knowledge regarding the identities of physiologically relevant retinol dehydrogenases, their enzymatic properties, and tissue distribution, and to discuss potential mechanisms for the regulation of the flux from retinol to retinaldehyde.
Topics: Animals; Biosynthetic Pathways; Humans; Retinaldehyde; Tretinoin
PubMed: 31861321
DOI: 10.3390/biom10010005 -
Methods in Enzymology 2022Carotenoids constitute an essential dietary component of animals and other non-carotenogenic species which use these pigments in both their modified and unmodified...
Carotenoids constitute an essential dietary component of animals and other non-carotenogenic species which use these pigments in both their modified and unmodified forms. Animals utilize uncleaved carotenoids to mitigate light damage and oxidative stress and to signal fitness and health. Carotenoids also serve as precursors of apocarotenoids including retinol, and its retinoid metabolites, which carry out essential functions in animals by forming the visual chromophore 11-cis-retinaldehyde. Retinoids, such as all-trans-retinoic acid, can also act as ligands of nuclear hormone receptors. The fact that enzymes and biochemical pathways responsible for the metabolism of carotenoids in animals bear resemblance to the ones in plants and other carotenogenic species suggests an evolutionary relationship. We will explore some of the modes of transmission of carotenoid genes from carotenogenic species to metazoans. This apparent relationship has been successfully exploited in the past to identify and characterize new carotenoid and retinoid modifying enzymes. We will review approaches used to identify putative animal carotenoid enzymes, and we will describe methods used to functionally validate and analyze the biochemistry of carotenoid modifying enzymes encoded by animals.
Topics: Animals; Carotenoids; Plants; Retinaldehyde; Retinoids
PubMed: 36008015
DOI: 10.1016/bs.mie.2022.05.005 -
Journal of Lipid Research 2021Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor... (Review)
Review
Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor cell outer segments. Following absorption of a photon, the 11-cis-retinal chromophore of visual pigment in photoreceptor cells isomerizes to all-trans-retinal. To maintain photosensitivity 11-cis-retinal must be replaced. At the same time, however, all-trans-retinal has to be handled so as to prevent nonspecific aldehyde activity. Some molecules of retinaldehyde upon release from opsin are efficiently reduced to retinol. Other molecules are released into the lipid phase of the disc membrane where they form a conjugate [N-retinylidene-PE (NRPE)] through a Schiff base linkage with PE. The reversible formation of NRPE serves as a transient sink for retinaldehyde that is intended to return retinaldehyde to the visual cycle. However, if instead of hydrolyzing to PE and retinaldehyde, NRPE reacts with a second molecule of retinaldehyde, a synthetic pathway is initiated that leads to the formation of multiple species of unwanted bisretinoid fluorophores. We report on recently identified members of the bisretinoid family, some of which differ with respect to the acyl chains associated with the glycerol backbone. We discuss processing of the lipid moieties of these fluorophores in lysosomes of retinal pigment epithelial cells, their fluorescence characters, and new findings related to light- and iron-associated oxidation of bisretinoids.
Topics: Retinaldehyde
PubMed: 32371567
DOI: 10.1194/jlr.TR120000742 -
Philosophical Transactions of the Royal... Oct 2009Absorption of a photon by visual pigments induces isomerization of 11-cis-retinaldehyde (RAL) chromophore to all-trans-RAL. Since the opsins lacking 11-cis-RAL lose... (Comparative Study)
Comparative Study Review
Absorption of a photon by visual pigments induces isomerization of 11-cis-retinaldehyde (RAL) chromophore to all-trans-RAL. Since the opsins lacking 11-cis-RAL lose light sensitivity, sustained vision requires continuous regeneration of 11-cis-RAL via the process called 'visual cycle'. Protostomes and vertebrates use essentially different machinery of visual pigment regeneration, and the origin and early evolution of the vertebrate visual cycle is an unsolved mystery. Here we compare visual retinoid cycles between different photoreceptors of vertebrates, including rods, cones and non-visual photoreceptors, as well as between vertebrates and invertebrates. The visual cycle systems in ascidians, the closest living relatives of vertebrates, show an intermediate state between vertebrates and non-chordate invertebrates. The ascidian larva may use retinochrome-like opsin as the major isomerase. The entire process of the visual cycle can occur inside the photoreceptor cells with distinct subcellular compartmentalization, although the visual cycle components are also present in surrounding non-photoreceptor cells. The adult ascidian probably uses RPE65 isomerase, and trans-to-cis isomerization may occur in distinct cellular compartments, which is similar to the vertebrate situation. The complete transition to the sophisticated retinoid cycle of vertebrates may have required acquisition of new genes, such as interphotoreceptor retinoid-binding protein, and functional evolution of the visual cycle genes.
Topics: Animals; Evolution, Molecular; Photoreceptor Cells, Invertebrate; Photoreceptor Cells, Vertebrate; Phylogeny; Retinaldehyde; Vertebrates; Vision, Ocular
PubMed: 19720652
DOI: 10.1098/rstb.2009.0043 -
Biochimica Et Biophysica Acta May 2014Cone visual pigments are visual opsins that are present in vertebrate cone photoreceptor cells and act as photoreceptor molecules responsible for photopic vision. Like... (Review)
Review
Cone visual pigments are visual opsins that are present in vertebrate cone photoreceptor cells and act as photoreceptor molecules responsible for photopic vision. Like the rod visual pigment rhodopsin, which is responsible for scotopic vision, cone visual pigments contain the chromophore 11-cis-retinal, which undergoes cis-trans isomerization resulting in the induction of conformational changes of the protein moiety to form a G protein-activating state. There are multiple types of cone visual pigments with different absorption maxima, which are the molecular basis of color discrimination in animals. Cone visual pigments form a phylogenetic sister group with non-visual opsin groups such as pinopsin, VA opsin, parapinopsin and parietopsin groups. Cone visual pigments diverged into four groups with different absorption maxima, and the rhodopsin group diverged from one of the four groups of cone visual pigments. The photochemical behavior of cone visual pigments is similar to that of pinopsin but considerably different from those of other non-visual opsins. G protein activation efficiency of cone visual pigments is also comparable to that of pinopsin but higher than that of the other non-visual opsins. Recent measurements with sufficient time-resolution demonstrated that G protein activation efficiency of cone visual pigments is lower than that of rhodopsin, which is one of the molecular bases for the lower amplification of cones compared to rods. In this review, the uniqueness of cone visual pigments is shown by comparison of their molecular properties with those of non-visual opsins and rhodopsin. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks.
Topics: Animals; Color Vision; Evolution, Molecular; Humans; Models, Molecular; Molecular Conformation; Opsins; Phylogeny; Retinal Cone Photoreceptor Cells; Retinaldehyde; Rhodopsin
PubMed: 24021171
DOI: 10.1016/j.bbabio.2013.08.009 -
Biochimica Et Biophysica Acta May 2014Fluorescence spectroscopy has become an established tool at the interface of biology, chemistry and physics because of its exquisite sensitivity and recent technical... (Review)
Review
Fluorescence spectroscopy has become an established tool at the interface of biology, chemistry and physics because of its exquisite sensitivity and recent technical advancements. However, rhodopsin proteins present the fluorescence spectroscopist with a unique set of challenges and opportunities due to the presence of the light-sensitive retinal chromophore. This review briefly summarizes some approaches that have successfully met these challenges and the novel insights they have yielded about rhodopsin structure and function. We start with a brief overview of fluorescence fundamentals and experimental methodologies, followed by more specific discussions of technical challenges rhodopsin proteins present to fluorescence studies. Finally, we end by discussing some of the unique insights that have been gained specifically about visual rhodopsin and its interactions with affiliate proteins through the use of fluorescence spectroscopy. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks.
Topics: Amino Acid Sequence; Animals; Cattle; Fluorescence Polarization; Fluorescent Dyes; Humans; Models, Molecular; Molecular Sequence Data; Photons; Protein Structure, Secondary; Protein Structure, Tertiary; Retinaldehyde; Rhodopsin; Spectrometry, Fluorescence
PubMed: 24183695
DOI: 10.1016/j.bbabio.2013.10.008