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BMC Oral Health

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Open Access 01-12-2022 | Diabetes | Research

PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose

Authors: Chunhui Zhu, Ying Zhao, Dandan Pei, Zhongbo Liu, Jin Liu, Ye Li, Shuchen Yu, Lingyan Ma, Junyi Sun, Ang Li

Published in: BMC Oral Health | Issue 1/2022

Abstract

Background

Oxidative stress mediated by hyperglycemia damages cell-reparative processes such as mitophagy. Down-regulation of mitophagy is considered to be a susceptible factor for diabetes mellitus (DM) and its complications. However, the role of mitophagy in DM-associated periodontitis has not been fully elucidated. Apoptosis of human gingival epithelial cells (hGECs) is one of the representative events of DM-associated periodontitis. Thus, this study aimed to investigate PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy activated in the process of high glucose (HG)-induced hGECs apoptosis.

Methods

For dose–response studies, hGECs were incubated in different concentrations of glucose (5.5, 15, 25, and 50 mmol/L) for 48 h. Then, hGECs were challenged with 25 mmol/L glucose for 12 h and 48 h, respectively. Apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL), caspase 9 and mitochondrial membrane potential (MMP). Subsequently, autophagy was evaluated by estimating P62, LC3 II mRNA levels, LC3 fluorescent puncta and LC3-II/I ratio. Meanwhile, the involvement of PINK1-mediated mitophagy was assessed by qRT-PCR, western blotting and immunofluorescence. Finally, hGECs were transfected with shPINK1 and analyzed by MMP, caspase 9 and annexin V-FITC apoptosis.

Results

The number of TUNEL-positive cells and caspase 9 protein were significantly increased in cells challenged with HG (25 mmol/L) for 48 h (HG 48 h). MMP was impaired both at HG 12 h and HG 48 h, but the degree of depolarization was more serious at HG 48 h. The autophagy improved as the amount of LC3 II increased and p62 decreased in HG 12 h. During this process, HG 12 h treatment induced PINK1-mediated mitophagy. PINK1 silencing with HG 12 h resulted in MMP depolarization and cell apoptosis.

Conclusions

These results suggested that loss of the PINK1 gene may cause mitochondrial dysfunction and increase sensitivity to HG-induced apoptosis of hGECs at the early stage. PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose.

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Title: PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose
Authors: Chunhui Zhu
Ying Zhao
Dandan Pei
Zhongbo Liu
Jin Liu
Ye Li
Shuchen Yu
Lingyan Ma
Junyi Sun
Ang Li
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Diabetes
Published in: BMC Oral Health / Issue 1/2022
Electronic ISSN: 1472-6831
DOI: https://doi.org/10.1186/s12903-022-02167-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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