Hypoxia Susceptibility Related to the Expression of Long Noncoding RNA as Regulators of Abraxas2 and Camk2d in the Heart Tissue of a Hypoxic Mouse Model

Abstract

Long noncoding RNAs (lncRNAs) play a regulatory role in hypoxic disease states, and identifying regulators that control gene expression in a hypoxic mouse model will introduce therapeutic targets and biomarkers of susceptibility to hypoxia. Previous studies show that CD‐1 and C57BL/6J mice are sensitive and resistant to hypoxic stress, respectively.CD‐1 and C57BL/6J mice were subjected to an intraperitoneal injection of SE‐175 (0.7 mg/kg) to induce a hypoxic response or 1x phosphate‐buffered saline (PBS) and then sacrificed after five hours in normoxic condition. RNA was extracted from heart tissue and analyzed in a microarray. Genomic BLAST was performed between the human genome and mice lncRNAs with ±2 fold change in expression (p < 0.05). The expression of several genes coding sequences and their associated lncRNAs were analyzed by qPCR.We identified two lncRNA 1500002F19Rik and LOC108168899 that were found in close proximity to the genes Abraxas2 and Camk2d, respectively. Microarray results suggested that 1500002F19Rik and LOC108168899 may play a role in the expression of Abraxas2 and Camk2d, respectively. The expression levels of Abraxas2, Camk2d, and their corresponding lncRNA were analyzed using qPCR. In mice treated with SE‐175, Abraxas2 and 1500002F19Rik were both upregulated in C57BL/6J mice, but neither displayed a significant change in CD‐1 mice. Camk2d and LOC108168899 were both upregulated in C57BL/6J mice, while Camk2d was upregulated in CD‐1 mice, but LOC108168899 showed no significant change.Because of the cytoprotective effects of Abraxas2 against oxidative stress, its upregulation and that of 1500002F19Rik in C57BL/6J mice provides a possible mechanism for their resistance to hypoxic stress. Camk2d is implicated in oxidative stress in cardiomyocytes and was upregulated to a higher magnitude in CD‐1 mice than in C57BL/6J mice, while LOC108168899 only showed increased expression in C57BL/6J mice. This suggests that LOC108168899 can be involved in downregulation of Camk2d that prevents further oxidative stress in C57BL/6J mice, so its lower expression in CD‐1 mice can lead to higher expression of Camk2d which may contribute to susceptibility to hypoxia.Support or Funding InformationThis project was supported by Touro University Nevada research grant.