Advanced oxidation protein products mediate human keratinocytes apoptosis by inducing cell autophagy through the mTOR–Beclin‐1 pathway. (16th September 2022)

• Record Type: Journal Article
• Authors: Ding, Ruoting; Liu, Zhongyuan; Tan, Jie; Sun, Baihui
• Is Part Of: Cell biochemistry and function. Volume 40:Number 8(2022)
• Page Start: 880
• Page End: 887
• Publication Date: 2022-09-16
• Subjects: advanced oxidation protein products -- apoptosis -- autophagy -- impaired wound healing -- oxidative stress; Cytochemistry -- Periodicals; Cell metabolism -- Periodicals; Biochemistry -- Periodicals; Cytology -- Periodicals; 572
• DOI: 10.1002/cbf.3749
• Languages: English
• ISSNs: 0263-6484

Abstract

Abstract: Excessive keratinocyte apoptosis leads to impaired wound healing. Recently, advanced oxidation protein products (AOPP) have been recognized as a marker of oxidative stress and a potent inducer of apoptosis. Previously, we have demonstrated that extracellular AOPP accumulation induced keratinocyte apoptosis, and we discovered that autophagy was involved. To further elucidate the role and mechanism of autophagy in AOPP‐induced‐apoptosis of keratinocytes, we treated HaCaT cells with increasing concentrations of AOPP‐human serum albumin or with AOPP‐human serum albumin for increasing durations. Cyto‐ID solution staining was used to assess cell autophagy using confocal laser scanning microscopy. Autophagy‐related protein interactions were investigated using western blot analysis. Exposure of HaCaT cells to AOPP decreased the expression of mammalian target of rapamycin (mTOR) and increased the expression of autophagy‐related proteins Beclin‐l and LC3, and eventually led to autophagy. Furthermore, an autophagy agonist significantly decreased the expression of apoptosis‐related proteins. Taken together, we showed that accumulation of extracellular AOPP induced autophagy in HaCaT cells via a reactive oxygen species‐dependent, mTOR–Beclin‐1‐mediated pathway, and that excessive autophagy‐mediated apoptosis, which resulted in delayed wound healing. Significance statement: Our previous studies have shown that advanced oxidation protein products induced apoptosis and mitochondrial dysfunction in human keratinocytes (HaCaT cells), which delay the wound healing process. Furthermore, we found that accumulation of extracellular AOPP can induce HaCaT cell autophagy through the ROS‐dependent, mTOR–Beclin‐1‐mediated pathway, which plays a very important role in regulating the process of apoptosis. Therefore, the results in this article may provide a target for elucidating the mechanism of delayed wound healing.