Disease relevance of Isoretinene A

• Furthermore, we studied the metabolism of 9-cis-RA and its transfer to the embryo following oral administration of the precursor 9-cis-retinaldehyde (9-cis-RAL; 100 mg/kg body weight) to pregnant mice and rats on gestational days 11 and 13, respectively [1].

High impact information on Isoretinene A

• The sensitization of photoreceptors promoted by 11-cis and 9-cis retinal is accompanied by the formation of rhodopsin and isorhodopsin, respectively [2].
• The spectral properties of rhodopsin in the large vesicles are similar to those of rhodopsin in photoreceptors; furthermore, bleached bovine rhodopsin is chemically regenerable with 9-cis retinal [3].
• In contrast, 9-cis-retinal was unable to restore intrinsic photosensitivity to melanopsin-ablated ipRGCs, arguing against melanopsin functioning merely in photopigment regeneration [4].
• The resonance Raman spectrum of unphotolyzed isorhodopsin formed by the addition of 9-cis-retinal to opsin was also measured [5].
• RALDH4 recognizes as substrate 9-cis-retinal generated in transfected cells by the short-chain dehydrogenases CRAD1, CRAD3, or RDH1, to reconstitute a path of 9-cis-retinoic acid biosynthesis in situ [6].

Biological context of Isoretinene A

• We detect at least one novel metabolite formed from both 9-cis-retinol and 9-cis-retinal that may play a role in inhibition of MCF7 cell proliferation [7].
• 9-cis-Retinal which occupies the binding site but does not reconstitute the chromophore was used as "caged retinal". Photoisomerization to the all-trans isomer triggers the reconstitution reaction [8].
• The partially-purified enzyme displayed allosteric kinetics for 9-cis-retinal [K0.5 = 5.2 microM, Hill coefficient = 1.4, Vmax = 7.85 nmol min-1 (mg of protein)-1] with the ratio Vmax/K0.5 = 1 [9].
• Administration of 9-cis-retinal increased the rate of dark adaptation and improved cone function in Rdh5(-/-)Rdh11(-/-) mice [10].
• These data extend the kinetic characterization of mRALDH1, provide insight into the possible role of this enzyme in the biogenesis of RAs, and should give useful information on the determination of amino acid residues that play crucial roles in the catalysis of all-trans and 9-cis retinal [11].

Anatomical context of Isoretinene A

• The addition of 9-cis-retinal to the media increased the amount of P23H, but not K296E, that was soluble and reached the plasma membrane [12].
• Treatment of labeled rod outer segments with 9-cis-retinal caused much of the non-rhodopsin label to be converted to isorhodopsin [13].
• In this work, we show that this enzyme also accounts for approximately 90% of the 9-cis-retinal dehydrogenase activity of rat liver cytosol [9].
• Rpe65 knockout mice (Rpe65-/-) are unable to synthesize the visual pigment chromophore 11-cis retinal; however, if these animals are reared in complete darkness, the rod photoreceptors accumulate a small amount of 9-cis retinal and its corresponding visual pigment isorhodopsin [14].
• Artificial pigments were prepared by regeneration of bleached gecko photoreceptor membranes with 9-cis-retinal, 9-cis-14-methylretinal, or 9-cis-alpha-retinal [15].

Associations of Isoretinene A with other chemical compounds

• The 2.3-kb cDNA encodes an aldehyde dehydrogenase of 487 amino acid residues, about two-orders of magnitude more active in vitro with 9-cis-retinal than with all-trans-retinal [6].
• Thereafter, a dose of either all-trans-retinol or 9-cis-retinal was injected intramuscularly, leading to the formation of a rhodopsin (lambdamax 504 nm) or isorhodopsin (lambdamax 487-493 nm) pigment, respectively [16].
• The results suggest that RDH4 may have a dual and tissue-specific role in oxidation of 9-cis- and 11-cis-isomers of retinol into 9-cis-retinal and 11-cis-retinal, respectively [17].
• Similarly to bacteriorhodopsin, proteorhodopsin that normally contains all-trans and 13-cis retinal is transformed at low pH to a species containing 9-cis retinal under continuous illumination at lambda > 530 nm [18].
• It would be predicted that 9-cis-retinoyl fluoride (1), an isostere of 9-cis-retinal, should be an active site directed, mechanism-based labeling agent of opsin, since a stable peptide bond should be formed instead of a Schiff base [19].

Gene context of Isoretinene A

• Treatment of Rpe65(-/-) mice with 9-cis-retinal lowered the TPLR threshold by 2.1 log units [20].
• Consistent with a role mediating inhibition of PC12 cell MAP kinases, NGF-stimulated ERK2 activation was suppressed considerably following pretreatment with fibroblast growth factor and 9-cis-retinal, two additional differentiation factors found to induce powerfully MKP-3 expression [21].
• cDNA cloning and expression of a human aldehyde dehydrogenase (ALDH) active with 9-cis-retinal and identification of a rat ortholog, ALDH12 [22].
• Rather, lumirhodopsin is converted to a new species, L' (11-cis and/or 9-cis retinal) which, on warming to room temperature, is indistinguishable from rhodopsin or isorhodopsin [23].
• Ligand-dependent conformational changes appear to influence a newly detected difference in the bathochromic shift exhibited by bovine and human CRALBP when complexed with 9-cis-retinal [24].

Analytical, diagnostic and therapeutic context of Isoretinene A

• Rod and cone visual function improved significantly in the mouse model of F. albipunctatus after treatment with 9-cis-retinal, suggesting a potential approach to slow the progression of cone dystrophy in affected humans [10].
• Absorption bands in the FTIR difference spectra of the educt and product of the reaction could be assigned by comparison with a 9-cis-retinal FTIR spectrum or an FT-Raman spectrum of BR and due to band shifts observed upon deuterium exchange [8].
• A high-performance liquid chromatographic (HPLC) procedure was developed to separate all-trans-, 13-cis-, 11-cis- and 9-cis-retinal isomers [25].

References