Prohibitin inhibits high glucose-induced apoptosis via maintaining mitochondrial function in human retinal capillary endothelial cells.

Content Provider	Europe PMC
Author	Zhang, Li He, Ying
Copyright Year	2020
Abstract	Mitochondrial dysfunction and excessive apoptosis of vascular endothelial cells play a critical role in the development of diabetic retinopathy (DR). Prohibitin (PHB), a significant regulator, maintains mitochondrial function and protects vascular endothelial cells against apoptosis. However, the mechanism underlying the protective effect of PHB on DR remains unclear. Since mitochondria are key regulators of vascular homeostasis, the present study aimed to investigate the molecular mechanism of PHB on maintaining mitochondrial function in human retinal capillary endothelial cells (HRCECs). To evaluate the role of PHB in cell apoptosis, HRCECs, transfected with or without PHB overexpression plasmid or small interfering RNA clones targeting PHB, were cultured in the presence of 5.5 mmol/l normal glucose (NG) or 30 mmol/l high glucose (HG). Subsequently, the apoptosis rate of HRCECs was determined using flow cytometry. The results showed that PHB was upregulated in HRCECs, while PHB knockdown promoted the generation of reactive oxygen species from mitochondria via inhibition of the activation of complex I. Additionally, the apoptosis rate of HRCECs in the HG group was notably enhanced compared with that in the NG group. Interestingly, PHB overexpression attenuated the increase in HG-mediated HRCEC apoptosis. Furthermore, treatment with HG upregulated expression of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase in vitro. The present study indicated that PHB could be a key modulator of mitochondrial homeostasis and could protect HRCECs against HG-induced apoptosis. Overall, the aforementioned findings provided experimental evidence supporting the potential protective effects of PHB on DR.
ISSN	17920981
Journal	Experimental and Therapeutic Medicine
Volume Number	23
PubMed Central reference number	PMC9121207
Issue Number	6
PubMed reference number	35607379
e-ISSN	17921015
DOI	10.3892/etm.2022.11354
Language	English
Publisher	D.A. Spandidos
Publisher Date	2022-05-05
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Zhang et al.
Subject Keyword	Prohibitin mitochondrial function apoptosis diabetic retinopathy
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Cancer Research