Biomaterial Database

Effects of reactive oxygen species on the biosynthesis of 12 (S)-hydroxyeicosatetraenoic acid in mouse epidermal homogenate. 1997

K Müller, and I Gawlik

Institute of Pharmacy, Pharmaceutical Chemistry I, University of Regensburg, Germany.

Arachidonic acid is converted to 12-hydroxyeicosatetraenoic acid (12-HETE) in a homogenate of mouse epidermal cells. When the epidermal homogenate was preincubated with scavengers of reactive oxygen species (ROS), catalase or superoxide dismutase, significantly larger amounts of 12-HETE were produced as compared to untreated controls, suggesting that 12-lipoxygenase is quite prone to inactivation by ROS and peroxides. Mouse epidermal homogenate was then exposed to nine different ROS-generating systems to study the effects of superoxide, hydrogen peroxide, singlet oxygen, hypochlorite, peroxyl radicals, and alkyl hydroperoxides on the enzyme activity. Analysis by chiral phase high performance liquid chromatography demonstrated that the 12-HETE biosynthesized from arachidonic acid by mouse epidermal homogenate was the 12 (S)-enantiomer and excludes oxidation of arachidonic acid by ROS in a nonspecific free radical mechanism which leads to racemic 12-HETE. ROS generated by the interaction of xanthine with xanthine oxidase strongly inhibited epidermal 12 (S)-HETE biosynthesis. A flux of 0.7 nmol of superoxide/min/ml of reaction medium resulted in more than 50% inhibition of epidermal 12-lipoxygenase activity. The decrease in 12 (S)-HETE biosynthesis appeared to involve both superoxide and hydrogen peroxide. The efficacy of the latter species was also documented by exposure of mouse epidermal 12-lipoxygenase to glucose and glucose oxidase, which resulted in similar inhibitory effects on 12 (S)-HETE biosynthesis. The presence of the iron chelator diethylenetriaminepentaacetic acid during incubation of epidermal 12-lipoxygenase with both the xanthine/xanthine oxidase or the glucose/glucose oxidase systems partially protected the enzyme against inhibition, indicating that hydroxyl radical contributes to the overall inhibitory effect. Also, organic hydroperoxides inhibited epidermal 12-lipoxygenase, whereas singlet oxygen, hypochlorite, and peroxyl radicals were not effective. The results of this study lead to the proposal that 12-lipoxygenase activity may be regulated by ROS such as hydrogen peroxides, superoxide, and hydroxyl radicals.

UI	MeSH Term	Description	Entries
D008773	Methylphenazonium Methosulfate	Used as an electron carrier in place of the flavine enzyme of Warburg in the hexosemonophosphate system and also in the preparation of SUCCINIC DEHYDROGENASE.	Phenazine Methosulfate,5-Methylphenazinium Methyl Sulfate,5 Methylphenazinium Methyl Sulfate,Methosulfate, Methylphenazonium,Methosulfate, Phenazine,Methyl Sulfate, 5-Methylphenazinium,Sulfate, 5-Methylphenazinium Methyl
D010100	Oxygen	An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.	Dioxygen,Oxygen-16,Oxygen 16
D010545	Peroxides	A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)	Peroxide
D011720	Pyrazoles	Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D002374	Catalase	An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA.	Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D005609	Free Radicals	Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.	Free Radical
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000875	Anthralin	An anthracene derivative that disrupts function and structure of MITOCHONDRIA and is used for the treatment of DERMATOSES, especially PSORIASIS. It may cause FOLLICULITIS.	1,8-Dihydroxy-9-anthrone,Dithranol,1,8,9-Anthracenetriol,1,8-Dihydroxy-9(10H)-anthracenone,Anthraforte,Anthranol,Cignolin,Cygnoline,Dihydroxyanthranol,Dithrocream,Ditranol FNA,Lasan,Micanol,Psoradrate,Psoricrème,1,8 Dihydroxy 9 anthrone,FNA, Ditranol
D000975	Antioxidants	Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues.	Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D012867	Skin	The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.