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Novel Role of Heterogeneous Nuclear Ribonucleoprotein E1 in Regulation of Apoptosis and Autophagy by a Triazole Derivative in Vascular Endothelial Cells.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2019 May 12; Vol. 15 (6), pp. 1299-1309. Date of Electronic Publication: 2019 May 12 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Vascular endothelial cell (VEC) apoptosis and autophagy play an important role in the maintenance of vascular homeostasis. However, the association of molecular mechanisms between vascular endothelial cell apoptosis and autophagy has not been clarified. Here, we identified a novel triazole derivative, JL014, which could inhibit human umbilical vein vascular endothelial cell (HUVEC) apoptosis induced by deprivation of serum and fibroblast growth factor 2 and maintain HUVEC survival by promoting autophagy. Importantly, JL014 increased the mRNA and protein level of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) in HUVECs. In addition, knockdown of hnRNP E1 by RNA interference inhibited the effects of JL014 on VEC apoptosis and autophagy. Furthermore, we investigated the effect of JL014 on the expression of HMBOX1, a key VEC apoptosis inhibitor and autophagy inducer by inhibiting mTOR signaling and the level of cleaved caspase-3. Our results demonstrated that JL014 enhanced mRNA transcription and increased protein synthesis of HMBOX1. JL014 also inhibited mTOR signaling and the cleaved caspase-3 level. Mechanistic studies revealed that hnRNP E1 could bind to the promoter and 5'UTR of HMBOX1 and active HMBOX1 expression. Therefore, our results firmly establish hnRNP E1 as a new regulator of VEC apoptosis and autophagy through mediating HMBOX1 expression, and opened the door to a novel therapeutic drug for related vascular diseases.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
- Subjects :
- Gene Expression Regulation
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Human Umbilical Vein Endothelial Cells
Humans
Protein Biosynthesis
Signal Transduction
TOR Serine-Threonine Kinases metabolism
Apoptosis
Autophagy
Endothelial Cells cytology
Heterogeneous-Nuclear Ribonucleoproteins physiology
Triazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 15
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31223288
- Full Text :
- https://doi.org/10.7150/ijbs.32677