Hypoxia and Hypoglycemia synergistically regulate mRNA stability

被引:14
作者
Carraway, Kristen R. [1 ]
Johnson, Ellen M. [1 ]
Kauffmann, Travis C. [2 ]
Fry, Nate J. [1 ]
Mansfield, Kyle D. [1 ]
机构
[1] East Carolina Univ, Brody Sch Med, Biochem & Mol Biol, Greenville, NC USA
[2] East Carolina Univ, Brody Sch Med, Greenville, NC USA
关键词
Hypoxia; hypoglycemia; mRNA stability; KHSRP; ENDOTHELIAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; COORDINATING GENE-EXPRESSION; ACUTE MYOCARDIAL-INFARCTION; MITOCHONDRIAL COMPLEX-III; POSTTRANSCRIPTIONAL REGULATION; INDUCIBLE FACTOR-1-ALPHA; CARDIAC MYOCYTES; BINDING PROTEINS; DIABETIC MICE;
D O I
10.1080/15476286.2017.1311456
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ischemic events, common in many diseases, result from decreased blood flow and impaired delivery of oxygen and glucose to tissues of the body. While much is known about the cellular transcriptional response to ischemia, much less is known about the posttranscriptional response to oxygen and glucose deprivation. The goal of this project was to investigate one such posttranscriptional response, the regulation of mRNA stability. To that end, we have identified several novel ischemia-related mRNAs that are synergistically stabilized by oxygen and glucose deprivation including VEGF, MYC, MDM2, and CYR61. This increase in mRNA half-life requires the synergistic effects of both low oxygen (1%) as well as low glucose ( 1g/L) conditions. Oxygen or glucose deprivation alone fails to initiate the response, as exposure to either high glucose (4g/L) or normoxic conditions inhibits the response. Furthermore, in response to hypoxia/hypoglycemia, the identified mRNAs are released from the RNA binding protein KHSRP which likely contributes to their stabilization.
引用
收藏
页码:938 / 951
页数:14
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