Osamu Hayaishi

Bio: Osamu Hayaishi is an academic researcher from Osaka Bioscience Institute. The author has contributed to research in topics: Prostaglandin & Prostaglandin D2. The author has an hindex of 81, co-authored 310 publications receiving 18514 citations.

Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine

Abstract: Caffeine, a component of tea, coffee and cola, induces wakefulness. It binds to adenosine A1 and A2A receptors as an antagonist, but the receptor subtype mediating caffeine-induced wakefulness remains unclear. Here we report that caffeine at 5, 10 and 15 mg kg(-1) increased wakefulness in both wild-type mice and A1 receptor knockout mice, but not in A2A receptor knockout mice. Thus, caffeine-induced wakefulness depends on adenosine A2A receptors.

The enzymatic cleavage of beta-carotene into vitamin A by soluble enzymes of rat liver and intestine

Abstract: That 13-carotene can serve as a precursor of vitamin A in mammals was demonstrated almost 40 years ago." 2 In spite of innumerable nutritional and chemical studies on this reaction, however, neither the pathway nor the mechanism of vitamin A formation has been clarified.3-5 With respect to the pathway of vitamin A formation, two major hypotheses have been suggested: (1) carotene is cleaved at the central 15-15' double bond to yield two molecules of vitamin A, and (2) carotene is cleaved peripherally to yield one molecule of vitamin A via a series of 13-apo-carotenals.4 Although f3-apo-carotenals have been found in nature,6 are highly effective biologically, and are converted to vitamin A in the mammal,4 they do not accumulate during the cleavage of ,8-carotene in vivo.7 The cleavage of ,8-carotene to vitamin A seemingly proceeds by an oxidative reaction. In isolated sections of intestine oxygen is required for the conversion of carotene to vitamin A,8 a requirement which correlates better with the cleavage reaction than with the absorption of carotene into gut slices.9 Furthermore, oxygen'8 is incorporated into vitamin A in the liver of carotene-treated animals when 0218 gas is used but not when H2018 is employed.'0 Purely chemical studies also accord with an oxidative cleavage mechanism."' 12 Although the intestine seems to be the major organ in the rat for carotene cleavage into vitamin A,7 1" the liver also catalyzes this reaction.'4 Interestingly, bile salts are necessary for the uptake and cleavage of carotene by gut slices,7 but are not required for cleavage in the liver.'4 In the present report an enzyme has been found in the supernatant solution of rat liver and intestine which converts 13-carotene into retinal and retinol as its sole products. Oxygen is required for the reaction, and the immediate product is retinal. The enzyme is inhibited by sulfhydryl binding reagents and by ferrous-ion chelating agents. The enzyme has been tentatively designated as 1-carotene 15-15' oxygenase. Materials and Methods.-Preparation of radioactive #-carotene: Sodium acetate J-C'4 was added to growing cultures of Phycomyces blakesleeanus, and the synthesized ,B-carotene was extracted and purified as previously described.'5 16 The three times recrystallized compound was greater than 98% pure, as judged by two-dimensional chromatography on silica gel thin-layer plates, and had a specific activity of 6560 cpm per Mg. The labeled ,B-carotene was stored in hexane in the presence of a-tocopherol in a red glass container in the cold. Just prior to each experiment a suitable quantity was purified through a small column of 6% water-deactivated alumina, dried in the dark under nitrogen, dissolved in 0.05 ml of 20% Tween 40 in distilled acetone, and made up to a suitable volume with 0.15 M tris-hydroxymethyl-aminomethane (Tris) buffer, pH 8.0. Preparation of organ homogenates: Male or female rats of the Wistar strain weighing 150-300 gm were anesthetized with ether, opened by midline incision, and the liver or kidneys were quickly removed and washed in saline. The upper half of the intestine was also removed, cut longitudinally to expose the mucosal surface, and washed in cold saline. Each tissue was minced on a cold Petri plate and homogenized with a loose-fitting, motor-driven glass homogenizer in 5 vol of cold 0.15

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

Abstract: The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...

Cyclooxygenases: Structural, cellular, and molecular biology

Abstract: ▪ Abstract The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.

Cyclooxygenases 1 and 2

Abstract: Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer’s disease.