scholarly journals Modulation of spectral properties and pump activity of proteorhodopsins by retinal analogues

2015 ◽  
Vol 467 (2) ◽  
pp. 333-343 ◽  
Author(s):  
Srividya Ganapathy ◽  
Odette Bécheau ◽  
Hanka Venselaar ◽  
Siebren Frölich ◽  
Jeroen B. van der Steen ◽  
...  
Keyword(s):  
Vitamin A ◽  
Spectral Properties ◽  
Proton Pumps ◽  
Pump Activity ◽  
Retinal Analogues ◽  
Vitamin A Derivative ◽  
Absorbance Band

Microbial proteorhodopsins are light-driven proton pumps, using the vitamin A derivative retinal as chromophore. We show that retinal analogues can shift their absorbance band with preservation of functionality. This may provide attractive opportunities in biotechnology, optogenetics and as potential sensors.

Multiple Congenital Malformations Associated with Maternal Isotretinoin Therapy

PEDIATRICS ◽  
1984 ◽  
Vol 74 (3) ◽  
pp. 428-430
Author(s):  
ELIZABETH DE LA CRUZ ◽  
SHYAN SUN ◽  
KAMTORN VANGVANICHYAKORN ◽  
FRANKIN DESPOSITO
Keyword(s):  
Vitamin A ◽  
Congenital Malformations ◽  
Cardiac Anomaly ◽  
Teratogenic Effects ◽  
Experimental Animals ◽  
Synthetic Vitamin ◽  
Extensive Information ◽  
Few Data ◽  
Vitamin A Derivative ◽  
Isotretinoin Therapy

Isotretinoin (Accutane), an oral synthetic vitamin A derivative, introduced in September 1982 by Roche Laboratories has been widely used in the treatment of recalcitrant cystic acne. Although there is extensive information regarding the teratogenic effects of excessive vitamin A in experimental animals,1 there are few data available on its possible effects in humans. We report a case of a preterm infant with microcephaly, microphthalmia, rudimentary pinnae, cardiac anomaly, and hepatocellular derangement born to a mother on isotretinoin therapy. This constellation of abnormalities mimicks the type of malformations seen in the animal models and is strongly suggestive of the teratogenicity of this drug to the human fetus.

Teratogenic Potential of Isotretinoin

1986 ◽  
Vol 8 (3) ◽  
pp. 68-94
Keyword(s):  
Animal Models ◽  
Vitamin A ◽  
Premature Infant ◽  
Congenital Anomalies ◽  
Pharmacologic Therapy ◽  
Multiple Congenital Anomalies ◽  
Keratolytic Agents ◽  
Teratogenic Potential ◽  
Vitamin A Derivative ◽  
Systemic Antibiotics

Pharmacologic therapy for acne, for the most part, consists of topical keratolytic agents and systemic antibiotics, but these modalities have had very little success in the treatment of cystic acne. In September 1982, isotretinoin, a Vitamin A derivative, was marketed for the treatment of recalcitrant acne and has proven to be efficacious. Because of the known teratogenicity of vitamin A in animal models, a manufacturer's warning was issued advising patients not to take this medication if they were pregnant or intended to become pregnant. Despite these warnings, there are reported cases of multiple congenital anomalies in infants born to mothers who took isotretinoin during the first half of pregnancy. Among the reported cases is a premature infant of 30 weeks' gestation born to a 22-year-old woman who used isotretinoin during her first 2 months of pregnancy.

scholarly journals Modified Rhodopsins From Aureobasidium pullulans Excel With Very High Proton-Transport Rates

2021 ◽  
Vol 8 ◽  
Author(s):  
Sabine Panzer ◽  
Chong Zhang ◽  
Tilen Konte ◽  
Celine Bräuer ◽  
Anne Diemar ◽  
...  
Keyword(s):  
Proton Pump ◽  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Aureobasidium Pullulans ◽  
Green Light ◽  
Maximal Activity ◽  
Site Directed Mutagenesis ◽  
Proton Pumps ◽  
C Terminus ◽  
Pump Activity

Aureobasidium pullulans is a black fungus that can adapt to various stressful conditions like hypersaline, acidic, and alkaline environments. The genome of A. pullulans exhibits three genes coding for putative opsins ApOps1, ApOps2, and ApOps3. We heterologously expressed these genes in mammalian cells and Xenopus oocytes. Localization in the plasma membrane was greatly improved by introducing additional membrane trafficking signals at the N-terminus and the C-terminus. In patch-clamp and two-electrode-voltage clamp experiments, all three proteins showed proton pump activity with maximal activity in green light. Among them, ApOps2 exhibited the most pronounced proton pump activity with current amplitudes occasionally extending 10 pA/pF at 0 mV. Proton pump activity was further supported in the presence of extracellular weak organic acids. Furthermore, we used site-directed mutagenesis to reshape protein functions and thereby implemented light-gated proton channels. We discuss the difference to other well-known proton pumps and the potential of these rhodopsins for optogenetic applications.

Synthesis of C11-to-C14 methyl-shifted all-trans-retinal analogues and their activities on human aldo-keto reductases

2020 ◽  
Vol 18 (25) ◽  
pp. 4788-4801
Author(s):  
Aurea Rivas ◽  
Raquel Pequerul ◽  
Vito Barracco ◽  
Marta Domínguez ◽  
Susana López ◽  
...  
Keyword(s):  
Vitamin A ◽  
Retinal Analogues

Human aldo-keto reductases (AKRs) are enzymes involved in the reduction, among other substrates, of all-trans-retinal to all-trans-retinol (vitamin A), thus contributing to the control of the levels of retinoids in organisms.

The spectral properties and photosensitivities of analogue photopigments regenerated with 10- and 14-substituted retinal analogues

1988 ◽  
Vol 233 (1270) ◽  
pp. 55-76 ◽  
Keyword(s):  
Schiff Base ◽  
Binding Site ◽  
Steric Hindrance ◽  
Visual Pigment ◽  
Spectral Properties ◽  
The Other ◽  
Porichthys Notatus ◽  
Counter Ion ◽  
Two Systems ◽  
Retinal Analogues

Analogues of 11- cis - and 9- cis -retinal with substitutions at positions 10 and 14 were used to regenerate analogue photopigments with two opsins: that of the transmuted (cone-like) 521-pigment of Gekko gekko and that of the rhodopsin of Porichthys notatus . The spectral absorbances and photosensitivities of the regenerated photopigments were determined and compared, first, between the two systems of analogue photopigments, and second, in the responses to the two opsins. Unlike the 10-fluoropigments, the comparable 14-compounds were significantly redshifted by 19–30 nm and their sensitivity to light was similar to that of the parent 11- cis - and 9- cis -pigments. These were the results for both analogue pigments. In contrast, the 10-pigments were spectrally located close to the wavelengths of the parent compounds and the photosensitivity was significantly reduced, especially in the case of the 9- cis -analogues. Evidence was obtained for a steric hindrance effect at position 14, for no regeneration was obtained when methyl or ethyl groups were at this carbon. In the 10-substituted retinals, steric hindrance was noted only for the gecko; only the fluorosubstituted, but not the chloro-, the methyl- or the ethyl-substituted, retinals reacted. With the fish opsin, pigments were regenerated with all but the ethyl-substituted retinal. The gecko opsin appears to have a more restricted binding site. Another feature of the gecko was related to the chloride bathochromic and hyperchromic effects, in which the 521-pigment prepared in a chloride-deficient state has a blue-shifted spectrum compared with the spectrum obtained after the addition of chloride, and its extinction is raised by the addition of chloride to give a mean ratio of 1.23 for the two extinctions, one with, the other without, added chloride. The 11- cis -10-F-analogue pigment gave both chloride effects and the hyperchromic ratio was the same as that recorded for the native visual pigment. In contrast, the pigment formed with 11- cis -14-F-retinal gave a hyperchromic ratio significantly greater than 1.23. A similar contrast in the responses to chloride was obtained with the analogue photopigments regenerated with the 9- cis -10-F- and 9- cis -14-F-chromophores. This difference between the two systems is interpreted as the result of a specific configurational feature of the gecko opsin when in the chloride-deficient state that is relevant to the binding of the retinal analogue. Together, the results point to a different interaction with the visual protein on the part of the 10- and 14-substituted retinals. The latter adjust the pigment colour by acting specifically at the opsin site of the negative counter ion responsible for adjusting the degree of protonation of the Schiff base nitrogen.

Hepatocanalicular injury associated with vitamin A derivative etretinate

1987 ◽  
Vol 32 (10) ◽  
pp. 1207-1211 ◽  
Author(s):  
Margaret R. Khouri ◽  
Scott H. Saul ◽  
Andrzej A. Dlugosz ◽  
Roger D. Soloway
Keyword(s):  
Vitamin A ◽  
Vitamin A Derivative

scholarly journals Retinoic acid controls the homeostasis of pre-cDC–derived splenic and intestinal dendritic cells

2013 ◽  
Vol 210 (10) ◽  
pp. 1961-1976 ◽  
Author(s):  
Christopher A. Klebanoff ◽  
Sean P. Spencer ◽  
Parizad Torabi-Parizi ◽  
John R. Grainger ◽  
Rahul Roychoudhuri ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Critical Role ◽  
Mucosal Injury ◽  
Immune Deficiencies ◽  
Radiation Induced ◽  
Essential Nutrient ◽  
Vitamin A Derivative ◽  
Regulatory Functions

Dendritic cells (DCs) comprise distinct populations with specialized immune-regulatory functions. However, the environmental factors that determine the differentiation of these subsets remain poorly defined. Here, we report that retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC (precursor of DC)–derived splenic CD11b+CD8α−Esamhigh DCs and the developmentally related CD11b+CD103+ subset within the gut. Whereas mice deprived of RA signaling significantly lost both of these populations, neither pre-DC–derived CD11b−CD8α+ and CD11b−CD103+ nor monocyte-derived CD11b+CD8α−Esamlow or CD11b+CD103− DC populations were deficient. In fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts resulted in near complete conversion of these cells into the CD11b+CD8α− subset, whereas transfer into vitamin A–deficient (VAD) hosts caused diversion to the CD11b−CD8α+ lineage. As vitamin A is an essential nutrient, we evaluated retinoid levels in mice and humans after radiation-induced mucosal injury and found this conditioning led to an acute VAD state. Consequently, radiation led to a selective loss of both RA-dependent DC subsets and impaired class II–restricted auto and antitumor immunity that could be rescued by supplemental RA. These findings establish a critical role for RA in regulating the homeostasis of pre-DC–derived DC subsets and have implications for the management of patients with immune deficiencies resulting from malnutrition and irradiation.

The Vitamin A derivative etretinate improves skin sclerosis in patients with systemic sclerosis

2004 ◽  
Vol 34 (1) ◽  
pp. 62-66 ◽  
Author(s):  
Takaharu Ikeda ◽  
Koji Uede ◽  
Hideo Hashizume ◽  
Fukumi Furukawa
Keyword(s):  
Systemic Sclerosis ◽  
Vitamin A ◽  
Skin Sclerosis ◽  
Vitamin A Derivative
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