SO₂inhalation modulates the expression of apoptosis-related genes in rat hippocampus via its derivativesin vivo

Abstract

The possible neurotoxicity of SO(2) 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 SO(2) 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 SO(2) 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 SO(2) 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 SO(2) derivative concentration and exposure time, and confirm that SO(2) 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 SO(2)-caused neurological insults, and imply that two major pathways associated with p53 and AP-1 might play important roles in the pathogenesis.

Endocannabinoid 2-arachidonoylglycerol protects inflammatory insults from sulfur dioxide inhalation via cannabinoid receptors in the brain

“…In the pathophysiology of these neurological diseases, a state of neuroinflammation accompanied by the alteration of the microvasculature function has been shown to be involved (Grammas et al, 2011;Farkas et al, 2000). In particular, our recent results confirm that acute SO 2 treatment causes neuroinflammation and microvasculature dysfunction, including the abnormal expression of inflammatory cytokines (inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule 1 (ICAM-1) and endothelial dysfunction related factor (endothelin 1 (ET-1) and endothelial nitric oxide synthase (eNOS)), and exacerbates cerebral ischemic responses (Sang et al, 2010;Yun et al, 2010). Specifically, neuroinflammation following chronic SO 2 inhalation above the environmental standard has been reported to impair neuronal behavior and repress memory-related kinase activation and the gene expression of glutamate receptors (Yao et al, 2015).…”

“…SO 2 is a widespread pro-inflammatory stimulus to the central nervous system (CNS) and has been largely studied as a risk factor for neurological disease (Shah et al, 2015;Weisskopf et al, 2015;Amancio and Nascimento, 2014;Yun et al, 2013). Although the accurate mechanisms underlying neurological disease induced by SO 2 exposure are not completely understood, recent studies indicate that oxidative stress, glial activation, neuroinflammation, and the following microvascular dysfunction may be attributed to the primary pathways (sang et al, 2010;yun et al, 2010;Block and Calderón-Garcidueñas, 2009). Moreover, inflammation in the vasculature has been shown to be involved in vasculature dysfunction-related diseases, such as ischemic stroke (Amancio and Nascimento, 2014) and hypertension (Cero et al, 2016).…”

Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis

“…However, there were no significant differences in the above parameters between the rats treated with SO 2 alone and the control rats. The results indicate that the concentration used in our experiment had no toxic effects on [44] and enhance the apoptosis of smooth muscle cells in spontaneously hypertensive rats (SHRs) [45] . As of yet, there are no reports indicating whether a low dose of SO 2 can induce PMN apoptosis while ameliorating lung injury.…”

In vivo screening to determine neurological hazards of nitrogen dioxide (NO2) using Wistar rats

“…Bax, Bak, Bid and Bad) proteins. These two kinds of protein function in harmony for the regulation of the apoptotic machinery, and are remarkably critical for cell fate [39]. Disturbance of the harmony happened after NO 2 exposure due to remarkably rising ratio of pro-apoptotic Bax protein to antiapoptotic Bcl-2.…”