Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Mitochondrial transcription factor A protects human retinal endothelial cell injury induced by hypoxia

Qilian Xie¹ , Xu Cao²

¹Department of Ophthalmology, The First Affiliated HospitalA292;and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, 471003; ²Department of Electrocardiogram, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, 471009, China.

For correspondence:- Qilian Xie Email: xql116@163.com Tel:+8637964830609

Received: 3 January 2017 Accepted: 20 May 2017 Published: 29 June 2017

Citation: Xie Q, Cao X. Mitochondrial transcription factor A protects human retinal endothelial cell injury induced by hypoxia. Trop J Pharm Res 2017; 16(6):1259-1266 doi: 10.4314/tjpr.v16i6.8

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the impact of mitochondrial transcription factor A (TFAM), as a modulator of NF-κB, on proliferation of hypoxia-induced human retinal endothelial cell (HREC), and the probable mechanism.

Methods: After exposure to hypoxia (1 % O₂) for 5 days, cell proliferation and cell cycle of HREC were measured by MTT (3-A288;4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay and flow cytometry. Cell signaling and mitochondrial DNA (mtDNA) copies were determined using real-time polymerase chain reaction and Western blot. NF-κB activity was evaluated by luciferase assay.

Results: TFAM expression decreased to 40 % in HREC under hypoxic condition (p < 0.05). MTT results revealed that TFAM facilitated HREC proliferation under hypoxia (p < 0.05). Moreover, flow cytometry demonstrated that TFAM promoted HREC proliferation by accelerating cell cycle (p < 0.05). Western blot and luciferase assay exhibited NF-κB activation in HREC after TFAM overexpression (p < 0.05). Finally, real-time PCR results showed that mtDNA and targeted genes of NF-κB were upregulated 3-fold in HREC after TFAM transfection under hypoxia (p < 0.05).

Conclusion: These results indicate that NF-κB activated by TFAM protects against hypoxia-induced HREC injury by accelerating cell cycle. The ability of TFAM to enhance NF-κB signaling may be part of the mechanism of hypoxia-induced cell injury. Thus, upregulation of TFAM may help to relieve diabetic retinopathy.

Keywords: Mitochondrial transcription factor A, NF-_4;B, Hypoxia, Human retinal endothelial cell, Diabetic retinopathy