Disease relevance of BETA-IONONE

• Pertussis toxin (a G protein inhibitor) also blocked beta-ionone-induced cell death [1].
• Our experiments show that in bleach-adapted rods beta-ionone causes a decrease in light sensitivity and dark current and an acceleration of the dim flash photoresponse and the rate constants of guanylyl cyclase and cGMP phosphodiesterase [2].
• These findings indicate that mechanisms other than impaired mevalonate synthesis mediate the anti-proliferative and cell cycle regulatory effects of beta-ionone and geraniol in human breast cancer cells [3].
• Among these 15 Streptomyces strains, S. fradiae Tü 27, S. arenae Tü 495, S. griseus ATCC 13273, S. violaceoniger Tü 38, and S. antibioticus Tü 4 and Tü 46 converted alpha-ionone to 3-hydroxy-alpha-ionone with significantly higher hydroxylation activity compared to that of beta-ionone [4].
• Apoptosis of human gastric adenocarcinoma cells induced by beta-ionone [5].

High impact information on BETA-IONONE

• Existence of a beta-ionone ring-binding site in the rhodopsin molecule [6].
• Rod cell death could be induced by forskolin (adenylate cyclase agonist), and conversely, beta-ionone-induced cell death could be blocked by cotreatment with SQ22536 (an adenylate cyclase inhibitor) [1].
• It was shown that the recombinant AtCCD7 protein catalyzes a specific 9-10 cleavage of beta-carotene to produce the 10 black triangle down-apo-beta-carotenal (C27) and beta-ionone (C13) [7].
• Modeling the locked chromophore analogs in the active site of rhodopsin suggests that the beta-ionone ring rotates but is largely confined within the binding site of the natural 11-cis-retinal chromophore [8].
• PhCCD1 is light-inducible and exhibits a circadian rhythm in both leaves and flowers. beta-Ionone emission by flowers occurred principally during daylight hours, paralleling PhCCD1 expression in corollas [9].

Biological context of BETA-IONONE

• Together, these observations indicate that in bleach-adapted rods beta-ionone activates phototransduction in the dark [2].
• These more polar products are presumed to result from multiple hydroxylations on the beta-ionone ring [10].
• From this recombinant strain the enzyme was purified by immuno-affinity chromatography and its cyclization activity characterized as a two-step reaction in which both sides of the lycopene molecule are cyclized to beta-ionone rings with the monocyclic gamma-carotene as an intermediate [11].
• The biotransformation of therapeutic retinoids containing the beta-ionone ring system is likely to involve the microsomal ATRA 4-hydroxylase P450 [12].
• From the N-BuOH soluble fraction of an MeOH extract of DENDRANTHEMA SHIWOGIKU, two new beta-ionone glucosides and roseoside were isolated, the structures of the new compounds elucidated were 2 and 3, respectively, on the basis of spectroscopic data and the results of an enzymic hydrolysis of 2 [13].

Anatomical context of BETA-IONONE

• Isolated salamander rod photoreceptors were exposed to bright light that bleached a significant fraction of their pigment, were allowed to recover to a steady state, and then were exposed to beta-ionone [2].
• The current view that the beta-ionone ring of the rhodopsin chromophore vacates its binding pocket within the protein early in the photocascade has been adopted in efforts to provide structural models of photoreceptor activation [14].
• Relative orientation between the beta-ionone ring and the polyene chain for the chromophore of rhodopsin in native membranes [15].
• The immunosuppression in cocaine + beta-ionone-treated mice was accompanied by a decrease in thymus weight and an increase in liver weight [16].
• To test the two hypotheses, we applied beta-ionone to partially bleached blue-sensitive rods and cones of salamander, two cells that couple the same cone-like opsin to either rod or cone transducin, respectively [17].

Associations of BETA-IONONE with other chemical compounds

• EPR spin trapping detection of carbon-centered carotenoid and beta-ionone radicals [18].
• It is shown here that 9-cis-retinoyl fluoride (1) reacts with opsin in a time-dependent fashion (t1/2 = 9 min at 25 microM 1) to form a new, nonbleachable pigment with a lambda max of approximately 365 nm. beta-Ionone competitively slows down the rate of the reaction [19].
• Rhodopsin was labeled by regeneration with the spin-labeled 9-cis retinal analogue in which the beta-ionone ring of retinal is replaced by the nitroxide tetramethyl-oxypyrrolidine ring [20].
• The induction of P-450IIB1/2, the only isozyme shown previously to be associated with the hepatotoxicity by cocaine, was demonstrated by Western immunoblotting to be induced by beta-ionone at doses as low as 300 mg/kg; but was less than the induction associated with phenobarbital [16].
• Both suppress 3-hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin interfered with the posttranslational processing of lamin B, an activity essential to assembly of daughter nuclei [21].

Gene context of BETA-IONONE

• Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1 [3].
• W(thereby the oxygen diffusion-concentration product) is larger in the meta II-enriched sample than in rhodopsin, indicating light-induced conformational changes of opsin around the beta-ionone binding site [20].
• However, the levels of TIMP-1 and TIMP-2 transcripts were elevated in cells treated with beta-ionone in a dose-dependent manner [22].
• CONCLUSION: beta-ionone can inhibit the proliferation of SGC-7901 cells, upregulate the expression of TIMP-1 and TIMP-2 expression, and may influence metastasis of cancer [22].
• The effects of beta-ionone on MMP-2 and MMP-9 activities in SGC-7901 cells were not observed [22].

Analytical, diagnostic and therapeutic context of BETA-IONONE

• Perfusion with beta-ionone also causes a partial reversal of the bleach-induced acceleration of cyclase velocity [23].
• Interactions of the beta-ionone ring with the protein in the visual pigment rhodopsin control the activation mechanism. An FTIR and fluorescence study on artificial vertebrate rhodopsins [24].
• The inductive effects of beta-ionone on P-450IA1/2 and P-450IIB1/2 proteins were confirmed by using Western immunoblotting with selective monoclonal antibodies [25].
• A slot blot analysis showed that the mRNA level was increased from 6 hr after treatment with beta-ionone in male rats and from 12 hr after treatment in female rats [26].
• Immunocytochemistry confirmed that all salamander rods contain one form of transducin, whereas all cones contain another. beta-Ionone enhanced pigment adaptation in blue-sensitive rods, but it also did so in blue- and UV-sensitive cones [17].

References