Search PubMed⌕ Search

Biomedical subjects

C J Epstein

Publications and source records attributed to C J Epstein.

312 records · Page 18Linked to original sources
PubMedDate not supplied

Attenuation of age-dependent oxidative damage to DNA and protein in brainstem of Tg Cu/Zn SOD mice.

Age-dependent accumulation of oxidative DNA and protein damage in brainstem and striatum was assessed in normal and transgenic (tg) mice which overexpress human Cu/Zn superoxide dismutase (h-SOD1). A marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (oxo8dG), was measured at 3, 12, and 18 months of age in control and tg mice. Cu/Zn SOD, but not MnSOD, activities in brainstems and striata from tg mice were increased compared to controls at all ages. At 18 months, oxo8dG levels were increased by 58% in brainstem and by 21% in striatum of control mice. In the tg mice, brainstem and striatal oxo8dG levels were increased to a lesser extent than in the corresponding controls. Protein oxidation (carbonyl content), was increased by 59% at 18 months in control brainstem, but not in striatum, and the increase was significantly attenuated in the tg mice. In summary, oxidative damage to DNA and protein increased with age in brainstem (and to a lesser extent in striatum), and augmented Cu/Zn SOD activity modified the extent of DNA and protein damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMedDate not supplied

Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss.

The participation of reactive oxygen species in aminoglycoside-induced ototoxicity has been deduced from observations that aminoglycoside-iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu/Zn-superoxide dismutase (h-SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h-SOD1 in inner ear tissues of transgenic C57BL/6-TgN[SOD1]3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg/kg body weight/day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin-treated group was 45-50 dB higher than in saline-injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside-induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention.

Animals↗
PubMedDate not supplied

Polypeptide induction by recombinant human IFN-gamma.

Partially purified natural human IFN-gamma has been shown to induce the synthesis of a set of unique polypeptides that are not induced by comparable amounts of IFN-alpha and IFN-beta. In addition, a set of polypeptides is induced in common by all three IFNs. The present study utilized a pure recombinant IFN-gamma and a monoclonal antibody against IFN-gamma to investigate whether the unique polypeptide-inducing properties previously reported are due to IFN-gamma itself. With the possible exception of two polypeptides, the results demonstrate conclusively that IFN-gamma is the sole molecular species responsible for the induction of all polypeptides, including those whose induction pattern is unique to IFN-gamma. Very high doses of IFN-alpha and IFN-beta induce some of the latter set of polypeptides to a limited extent. Thus the differential effects of IFN-gamma compared to IFN-alpha and IFN-beta are, in part, quantitative rather than qualitative in nature.

Antibodies, Monoclonal↗