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Titolo:
The effect of aliphatic, naphthenic, and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat brain synaptosome fraction: the involvement of calcium, nitric oxide synthase, mitochondria, and phospholipase A
Autore:
Myhre, O; Fonnum, F;
Indirizzi:
Norwegian Def Res Estab, Div Protect & Mat, N-2027 Kjeller, Norway Norwegian Def Res Estab Kjeller Norway N-2027 at, N-2027 Kjeller, Norway Norwegian Acad Sci & Letters, Statoil, Oslo, Norway Norwegian Acad Sci & Letters Oslo Norway Letters, Statoil, Oslo, Norway
Titolo Testata:
BIOCHEMICAL PHARMACOLOGY
fascicolo: 1, volume: 62, anno: 2001,
pagine: 119 - 128
SICI:
0006-2952(20010701)62:1<119:TEOANA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED PROTEIN-KINASE; PERMEABILITY TRANSITION PORE; HUMAN NEUTROPHIL GRANULOCYTES; CEREBELLAR GRANULE NEURONS; SPIRIT INHALATION EXPOSURE; LONG-TERM POTENTIATION; C-DEPENDENT PROCESSES; WHITE SPIRIT; OXIDATIVE STRESS; TYROSINE KINASE;
Keywords:
reactive oxygen species; reactive nitrogen species; aliphatic, naphthenic, and aromatic hydrocarbons; rat brain synaptosomes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
80
Recensione:
Indirizzi per estratti:
Indirizzo: Myhre, O Norwegian Def Res Estab, Div Protect & Mat, POB 25, N-2027 Kjeller, Norway Norwegian Def Res Estab POB 25 Kjeller Norway N-2027 ler, Norway
Citazione:
O. Myhre e F. Fonnum, "The effect of aliphatic, naphthenic, and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat brain synaptosome fraction: the involvement of calcium, nitric oxide synthase, mitochondria, and phospholipase A", BIOCH PHARM, 62(1), 2001, pp. 119-128

Abstract

This study investigated the effects of C7 and C9 aliphatic (n-heptane, n-nonane), naphthenic (methylcyclohexane, 1,2,4-trimethylcyclohexane (TMCH)) and aromatic (toluene, 1,2,4-trimethylbenzene (TMB)) hydrocarbons on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in rat brain synaptosome fraction. Methyl mercury (MeHg) was included as a positive control. Exposure of the synaptosomes to the hydrocarbons produced a concentration-dependent linear increase in the formation of the fluorescence of 2',7'-dichlorofluorescein (DCF) as a measure of the production ofROS and RNS. Formation of RNS was demonstrated by preincubation of the synaptosome fraction with the neuronal nitric oxide synthase (nNOS) inhibitor N omega -nitro-L-arginine methyl ester (L-NAME), which reduced the MeHg andTMCH-stimulated fluorescence by 51% and 65%, respectively. The naphthenic hydrocarbon TMCH showed the strongest potential for ROS and RNS formation in rat brain synaptosomes, followed by TMB, toluene, n-nonane, n-heptane, and methylcyclohexane, respectively. TMCH was selected for mechanistic studies of the formation of ROS. Both MeHg and TMCH induced an increase in intracellular calcium concentration [Ca2+](i) as measured with Fura-2. Blockade of voltage-dependent Ca2+ channels with lanthanum prior to stimulation with MeHg and TMCH led to a reduction in the ROS/RNS formation of 72% and 70%, respectively. Furthermore, addition of cyclosporin A (CSA), a blocker of themitochondrial permeability transition pore (MTP), lowered both the MeHg and TMCH-elevated DCF fluorescence by 72% and 59%. Preincubation of the synaptosome fraction with the protein tyrosine kinase inhibitor genistein lowered the MeHg and TMCH-stimulated fluorescence by 85% and 91%, respectively. Addition of the extracellular signal-regulated protein kinase (MEK)-1 and -2inhibitor U0126 reduced the fluorescence stimulated by MeHg and TMCH by 62% and 63%. Furthermore, the protein kinase C inhibitor bisindolylmaleimide reduced the fluorescence stimulated by MeHg and TMCH by 52% and 56%. The compound 1-(6-[17beta-3-methoxyestra-1,3,5(10)-trien-17-yl]-aminohexyl)-1H-pyrrole-2,5-dione (U73122), which inhibits phospholipase C, was shown to decrease the ROS and RNS formation induced by MeHg and TMCH by 49% and 64%, respectively. The phospholipase A(2) (PLA(2)) inhibitor 7,7-dimethyl eicosadienoic acid (DEDA) reduced fluorescence in response to MeHg and TMCH by 49% and 54%. Simultaneous addition of L-NAME, CSA, and DEDA to the synaptosome fraction totally abolished the DCF fluorescence. In conclusion, C7 and C9 aliphatic, naphthenic, and aromatic hydrocarbons stimulated formation of ROS and RNS in rat brain synaptosomes. The naphthenic hydrocarbon TMCH stimulated formation of ROS and RNS in the synaptosomes through Ca2+-dependent activation of PLA(2) and nNOS, and through increased transition permeability ofthe MTP. Exposure of humans to the naphthenic hydrocarbon TMCH may stimulate formation of free radicals in the brain, which may be a key factor leading to neurotoxicity. (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 09:15:27