Showing papers by "Yuichiro J. Suzuki published in 2007"
TL;DR: A promoter region of the mouse gata4 gene that is 1,000 bp immediately upstream from the transcriptional start site is identified, suggesting that the proximal 250-bp region contains important transcriptional regulatory sites and is responsible for the enhanced GATA activity.
Abstract: Intermittent hypoxia (IH) with repeated episodes of hypoxia-normoxia cycle has been shown to exert preconditioning-like cardioprotective effects. To understand the mechanism of these events, we inv...
45 citations
TL;DR: In a mouse model of OSA, it is found that IH causes time-dependent alterations of the susceptibility of the heart to oxidative stress, and exposure to prolonged IH allowed reversal of the enhancement of myocardial damage.
Abstract: Obstructive sleep apnea (OSA) is associated with cardiovascular diseases such as hypertension through mechanisms involving intermittent hypoxia (IH). However, it is not yet clear whether IH directly affects the heart. In a mouse model of OSA, we found that IH causes time-dependent alterations of the susceptibility of the heart to oxidative stress. Acute IH can exert preconditioning-like cardioprotection, in part, through the transcriptional activation of genes such as bcl-x(L) and gata4. We cloned the mouse gata4 promoter and identified an IH-responsive region. The exposure of mice to prolonged IH results in the increased susceptibility of the heart to ischemia-reperfusion injury by increasing the oxidative stress status. This might resemble conditions of OSA patients. In our mouse model, further exposure to prolonged IH allowed reversal of the enhancement of myocardial damage. Understanding the complex effects of IH on the heart should help ultimately to develop therapeutic strategies against OSA-induced complications.
41 citations
TL;DR: Inducers of pulmonary hypertension enhance anti-apoptotic Bcl-x(L) gene transcription, which can be suppressed by targeting gata4 gene transcription and established that SNP targets the 250 proximal region of the gATA4 promoter and suppresses its gene transcription.
Abstract: Pulmonary hypertension is characterized by thickened pulmonary arterial walls due to increased number of pulmonary artery smooth muscle cells (PASMC). Apoptosis of PASMC may play an important role in regulating the PASMC number and may be useful for reducing pulmonary vascular thickening. The present study examined the regulation of an anti-apoptotic protein Bcl-xL. Bcl-xL expression was found to be increased in the pulmonary artery of chronic hypoxia–treated rats with pulmonary vascular remodeling. Adenovirus-mediated gene transfer of Bcl-xL indeed showed that this protein has anti-apoptotic activities in PASMC. Treatment of remodeled pulmonary artery with sodium nitroprusside (SNP) reduced Bcl-xL expression by targeting the bcl-xL promoter. The bcl-xL promoter contains two GATA elements, and SNP decreases the GATA-4 DNA-binding activity. Overexpression of GATA-4 attenuated the SNP-mediated suppression of Bcl-xL expression, providing direct evidence for the role of GATA-4 in Bcl-xL gene transcription. We established that SNP targets the 250 proximal region of the gata4 promoter and suppresses its gene transcription. Thus, inducers of pulmonary hypertension enhance anti-apoptotic Bcl-xL gene transcription, which can be suppressed by targeting gata4 gene transcription.
36 citations
4 citations
4 citations