SO₂ inhalation modulates the expression of apoptosis-related genes in rat hippocampus via its derivatives in vivo

Abstract

The possible neurotoxicity of SO₂ has been implicated by determining morphological change, oxidative stress, DNA damage and membrane channel alteration in previous studies, however, its detailed mechanisms remain unclear. In the present study, we investigated SO₂ inhalation-induced effects on the transcription and translation of several apoptosis-related genes (p53, bax, bcl-2, c-fos, and c-jun) in rat hippocampus, using real-time RT-PCR analysis and western blotting technique, respectively. The results demonstrate that SO₂ statistically increased p53 expression and the ratio of bax to bcl-2 in a concentration-dependent manner. Also, mRNA and protein levels of c-fos and c-jun significantly elevated in proportion to exposure concentration. Then, we treated primary cultured hippocampal neurons with SO₂ derivatives (bisulfite and sulfite, 3:1 M/M), and examined mRNA levels of above genes. The results show that P53, c-fos, c-jun mRNA expression and the ratio of bax to bcl-2 augmented as functions of SO₂ derivative concentration and exposure time, and confirm that SO₂ affected the transcription and translation process of apoptosis-related genes in central nervous system via its derivatives in vivo. The present data provide further evidence for SO₂-caused neurological insults, and imply that two major pathways associated with p53 and AP-1 might play important roles in the pathogenesis.

Keywords::

• SO₂
• SO₂ derivatives
• hippocampus
• primary cultured hippocampal neuron
• apoptosis-related gene