IngentaConnect ALTERED LEVEL OF APURINIC/APYRIMIDINIC ENDONUCLEASE/REDOX FACTOR-...

Authors: Yalcin, Ayfer¹; Kanit, Lutfiye²; Durmaz, Guliz¹; Sargin, Sehnaz³; Terek, Cosan H⁴; Tanyolac, Bahattin³

Source: Clinical and Experimental Pharmacology and Physiology, Volume 32, Number 8, August 2005 , pp. 611-614(4)

Abstract:

SUMMARY

1. Accumulated clinical evidence suggests that selective oestrogen receptor modulators (SERM), such as raloxifene, may be neuroprotective. Oxidative stress is a likely molecular mechanism in the neurotoxicity of kainic acid (KA), an excitotoxic substance. The expression levels of the apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) gene seem to correlate with cellular sensitivity to reactive oxygen species (ROS) and a reduction in the expression of APE/Ref-1 may cause oxidative DNA damage.

2. The aim of the present study was to assess the effects of KA and raloxifene on the level of APE/Ref-1 mRNA in the hippocampus of ovariectomized rats. The expression of the APE/Ref-1 gene was quantified using reverse transcription followed by real-time polymerase chain reaction.

3. The results show that the level of APE/Ref-1 mRNA increased significantly in raloxifene-treated rats. However, raloxifene treatment did not affect the seizure severity induced by KA. We also observed that raloxifene treatment against simultaneous KA injection maintained the increased level of APE/Ref-1 mRNA in the hippocampus.

4. Therefore, the results of the present study seem to support previous data suggesting the potential significance of raloxifene in neuroprotection.

Keywords: APE; Ref-1; hippocampus; kainic acid; ovariectomy; raloxifene; real-time polymerase chain reaction; selective oestrogen receptor modulators

Document Type: Original article

DOI: 10.1111/j.0305-1870.2005.04239.x

Affiliations: 1: Department of Biochemistry, Faculty of Pharmacy, 2: Department of Physiology and 3: Department of Bioenginering, Institute of Science and Technology, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey 4: Department of Obstetrics and Gynecology, Faculty of Medicine and

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ALTERED LEVEL OF APURINIC/APYRIMIDINIC ENDONUCLEASE/REDOX FACTOR-1 (APE/Ref-1) mRNA IN THE HIPPOCAMPUS OF OVARIECTOMIZED RATS TREATED BY RALOXIFENE AGAINST KAINIC ACID