Biomaterial Database

Heme-oxygenase-1 promotes polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress and dopaminergic cell injury. 2006

Donna W Lee, and Robert M Gelein, and Lisa A Opanashuk

Department of Environmental Medicine, University of Rochester of School of Medicine and Dentistry, Rochester, New York 14642, USA.

Dopaminergic (DAergic) systems have been identified as putative targets for polycholorinated biphenyl (PCB) actions. However, the precise mechanisms leading to neurotoxicity are unresolved. Reactive oxygen species (ROS) were recently shown to mediate injury in DAergic MN9D cells following exposure to Aroclor 1254 (A1254), a commercial PCB mixture. The oxidative stress response in DAergic cells included a persistent expression of heme oxygenase-1 (HO-1). This study tested the hypothesis that a sustained PCB-induced HO-1 response leads to abnormally high Fe levels, which generates ROS production and mediates death in the MN9D DAergic cell model. Accordingly, results indicated that A1254 augmented intracellular Fe levels in MN9D cells after 24 h. Fe chelation by desferoxamine or pharmacologic inhibition of HO activity with tin-protoporphyrin reduced Fe accumulation, ROS production, and cytotoxicity following A1254 exposure. HO-1 over-expression predisposed MN9D DAergic cells to enhanced ROS production and cell death in response to PCBs. Conversely, antisense inhibition of HO-1 expression prevented PCB-induced ROS production and cell death. These observations suggest that enhanced HO-1 catalytic activity and subsequent liberation of Fe participate in neurotoxic DAergic cell injury caused by A1254 exposure in vitro.

UI	MeSH Term	Description	Entries
D007501	Iron	A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.	Iron-56,Iron 56
D008665	Metalloporphyrins	Porphyrins which are combined with a metal ion. The metal is bound equally to all four nitrogen atoms of the pyrrole rings. They possess characteristic absorption spectra which can be utilized for identification or quantitative estimation of porphyrins and porphyrin-bound compounds.	Metalloporphyrin
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011524	Protoporphyrins	Porphyrins with four methyl, two vinyl, and two propionic acid side chains attached to the pyrrole rings. Protoporphyrin IX occurs in hemoglobin, myoglobin, and most of the cytochromes.
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003676	Deferoxamine	Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.	Desferrioxamine,Deferoxamine B,Deferoxamine Mesilate,Deferoxamine Mesylate,Deferoxamine Methanesulfonate,Deferoximine,Deferrioxamine B,Desferal,Desferioximine,Desferrioxamine B,Desferrioxamine B Mesylate,Desferroxamine,Mesilate, Deferoxamine,Mesylate, Deferoxamine,Mesylate, Desferrioxamine B,Methanesulfonate, Deferoxamine
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004785	Environmental Pollutants	Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS.	Environmental Pollutant,Pollutant,Pollutants,Pollutants, Environmental,Pollutant, Environmental
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme