Catechols produce reactive oxygen species (ROS) and induce oxidative DNA damage through reduction-oxidation reactions with metals such as copper. Here, we examined oxidative DNA damage by neurotransmitter catecholamines in the presence of copper or iron and evaluated the effects of this damage on gene expression in vitro. Dopamine induced strand breaks and base oxidation in calf thymus DNA in the presence of Cu(II) or Fe(III)-NTA (nitrilotriacetic acid). The extent of this damage was greater for Cu(II) than for Fe(III)-NTA. For the DNA damage induced by dopamine, the responsible reactive species were hydrogen peroxide and Cu(I) for Cu(II) and hydroxyl radicals and Fe(II) for Fe(III)-NTA. Cu(II) induced DNA conformational changes, but Fe(III)-NTA did not in the presence of dopamine. These differences indicate different modes of action between Cu and Fe-NTA with regard to the induction of DNA damage. Expression of the lacZ gene coded on plasmid DNA was inhibited depending on the extent of the oxidative damage and strand breaks. Endogenous catecholamines (dopamine, adrenaline, and noradrenaline) were more potent than catechols (no aminoalkyl side chains) or 3,4-dihydroxybenzylamine (aminomethyl side chain). These results suggest that the metal-mediated DNA damage induced by dopamine disrupts gene expression, and leukoaminochromes (further oxidation products of O-quinones having aminoethyl side chain) are involved in the DNA damage. These findings indicate a possibility that metal (especially iron and copper)-mediated oxidation of catecholamines plays an important role in the pathogenesis of neurodegenerative disorders including Parkinson's disease.
We investigated the effects of redecoration of a hospital isolation room with natural materials on thermoregulatory, cardiovascular and hormonal parameters of healthy subjects staying in the room. Two isolation rooms with almost bilaterally-symmetrical arrangements were used. One room (RD) was redecorated with wood paneling and Japanese paper, while the other (CN) was unchanged (with concrete walls). Seven healthy male subjects stayed in each room for over 24 h in the cold season. Their rectal temperature (T(re)) and heart rate, and the room temperature (T(a)) and relative humidity were continuously measured. Arterial blood pressures, arterial vascular compliance, thermal sensation and thermal comfort were measured every 4 h except during sleeping. Blood was sampled after the stay in the rooms. In RD, T(a) was significantly higher by about 0.4 degrees C and relative humidity was lower by about 5% than in CN. Diurnal T(re) levels of subjects in RD significantly differed from those in CN, i.e., T(re)s were significantly higher in RD than in CN especially in the evening. In RD, the subjects felt more thermally-comfortable than in CN. Redecoration had minimal effects on cardiovascular parameters. Plasma levels of catecholamines and antidiuretic hormone did not differ, while plasma cortisol level was significantly lower after staying in RD than in CN by nearly 20%. The results indicate that, in the cold season, redecoration with natural materials improves the thermal environment of the room and contributes to maintaining core temperature of denizens at preferable levels. It also seems that redecoration of room could attenuate stress levels of isolated subjects.
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