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Publication : Role of DRAM1 in mitophagy contributes to preeclampsia regulation in mice.

First Author  Chen G Year  2020
Journal  Mol Med Rep Volume  22
Issue  3 Pages  1847-1858
PubMed ID  32582984 Mgi Jnum  J:306503
Mgi Id  MGI:6708487 Doi  10.3892/mmr.2020.11269
Citation  Chen G, et al. (2020) Role of DRAM1 in mitophagy contributes to preeclampsia regulation in mice. Mol Med Rep 22(3):1847-1858
abstractText  Preeclampsia (PE) is a complication during pregnancy that is diagnosed by a new onset of hypertension and proteinuria. Although the pathogenesis of PE is not fully understood, a growing body of evidence indicates that oxidative stress and mitochondrial dysfunction might contribute to the progression of PE. Therefore, the aim of the present study was to determine the role of mitophagy in mitochondrial dysfunction and oxidative stress in PE, and to evaluate the role of DNA damageregulated autophagy modulator 1 (DRAM1) in the development of PE. First, a mouse model of PE induced by hypoxiainducible factor 1alpha was established, and high levels of oxidative stress, apoptosis and mitochondrial dysfunction were found in the placentas of PE mice. Additionally, the placentas of PE mice exhibited decreased mitophagy and significantly decreased DRAM1 expression. To further explore the role of DRAM1 in mitophagy, DRAM1 was overexpressed in the placental tissues of PE mice, and this overexpression effectively improved the symptoms of PE mice and significantly reduced blood lipid and urine protein levels. DRAM1 overexpression also improved mitochondrial function and reduced oxidative stress in the placentas of PE mice. In addition, the overexpression of DRAM1 improved mitochondrial fusion and fission, and enhanced mitophagy. Altogether, these results indicated a key role for DRAM1 in mitophagy that contributed to the regulation of PE. To the best of the authors' knowledge, the present study provided the first evidence of a role for DRAM1 in PE, and offered novel insight into the pathophysiological mechanisms of PE.
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