2. Academic Validation
  3. The effect of TSPO transmembrane transport-mediated paeonol mitochondrial antioxidant on dexamethasone-induced mitochondrial abnormalities, oxidative stress damage, and apoptosis in SV40-MES-13 cells

The effect of TSPO transmembrane transport-mediated paeonol mitochondrial antioxidant on dexamethasone-induced mitochondrial abnormalities, oxidative stress damage, and apoptosis in SV40-MES-13 cells

  • Exp Cell Res. 2025 Jul 15;450(2):114674. doi: 10.1016/j.yexcr.2025.114674.
Yuqi Yang 1,  Yiye Zhou 2,  Xiaoqing Zhao 3,  Ruonan Dang 4,  Ping Fan 5,  Fenglan Feng 6,  Xingrong Wang 7,  Ning Zhang 8,  Jinjin Deng 9,  Meng Wei 10,  Xinglan Huang 11,  Caifeng Huang 12,  Suiying Zhang 13,  Yuqiong Deng 14,  Chunming Chen 15,  Peng Yan 16,  Xinhua Xia 17,  Sheng Liu 18,  Xiping Cheng 19
Affiliations

Affiliations

  • 1 The Affiliated Traditional Chinese Medicine Hospital of Guangzhou Medical University, No. 95 Tiankun 3rd Road, Tianhe District, Guangzhou, 510182, Guangdong Province, China. Electronic address: yangyangyuanling@163.com.
  • 2 The Affiliated Traditional Chinese Medicine Hospital of Guangzhou Medical University, No. 95 Tiankun 3rd Road, Tianhe District, Guangzhou, 510182, Guangdong Province, China. Electronic address: 2019620501@gzhmu.ed.cn.
  • 3 The Affiliated Traditional Chinese Medicine Hospital of Guangzhou Medical University, No. 95 Tiankun 3rd Road, Tianhe District, Guangzhou, 510182, Guangdong Province, China. Electronic address: 371361151@qq.com.
  • 4 The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: d2600696@163.com.
  • 5 The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: fanping18@163.com.
  • 6 The Key Laboratory of Advanced Interdisciplinary Studies, First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease, 620 Renmin North Road, Yuexiu District, Guangzhou, 510250, Guangdong Province, China. Electronic address: phoenix.feng@gzlab.ac.cn.
  • 7 The Key Laboratory of Advanced Interdisciplinary Studies, First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease, 620 Renmin North Road, Yuexiu District, Guangzhou, 510250, Guangdong Province, China. Electronic address: 1349927497@qq.com.
  • 8 Department of Dermatology, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: 1224853398@qq.com.
  • 9 Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: djj997296774@163.com.
  • 10 Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: mw12291997@163.com.
  • 11 Department of Dermatology, Guangzhou Twelfth People's Hospital, 1 Tianqiang Road, Tianhe District, Guangzhou, 510405, Guangdong Province, China. Electronic address: 18826247179@163.com.
  • 12 Department of Dermatology, Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: hcfyxq@126.com.
  • 13 Department of Dermatology, Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: 651458233@qq.com.
  • 14 Department of Dermatology, Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: 1558856954@qq.com.
  • 15 The Affiliated Traditional Chinese Medicine Hospital of Guangzhou Medical University, No. 95 Tiankun 3rd Road, Tianhe District, Guangzhou, 510182, Guangdong Province, China. Electronic address: 3305553121@qq.com.
  • 16 The Key Laboratory of Advanced Interdisciplinary Studies, First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease, 620 Renmin North Road, Yuexiu District, Guangzhou, 510250, Guangdong Province, China. Electronic address: 343304930@qq.com.
  • 17 The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: star1124@163.com.
  • 18 The Key Laboratory of Advanced Interdisciplinary Studies, First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease, 620 Renmin North Road, Yuexiu District, Guangzhou, 510250, Guangdong Province, China. Electronic address: 792238980@qq.com.
  • 19 The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang West Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, China. Electronic address: chengxiping2007@gzhmu.edu.cn.
PMID: 40683587 DOI: 10.1016/j.yexcr.2025.114674
Abstract

Dexamethasone (DEX) can induce pathological kidney injury but is still a first-line therapeutic agent; thus, elucidating the mechanism of DEX-induced kidney injury and developing targeted therapies to mitigate its effects are imperative. The aim of this study was to elucidate the mitochondrial targeting mechanism of the natural plant compound paeonol on DEX-induced mesangial cell injury. To achieve this, we employed RT q-PCR and Western blot analyses to quantify gene/protein expression, flow cytometry for Apoptosis assessment (Annexin V/PI staining) and mtROS detection (MitoSOX Red), JC-1 probe for mitochondrial membrane potential (ΔΨm) measurement, and High-sensitivity structured illumination microscopy (HiS-SIM) imaging for ultrastructural analysis. ATP synthesis assays and malondialdehyde (MDA) quantification were used to evaluate mitochondrial function and lipid peroxidation, respectively, while Mn-SOD activity was determined via enzymatic assays. Paeonol counteracted these effects via four mechanisms: restoration of mitochondrial ultrastructure. reactivation of MRCC IV activity, reduction of mtROS and malondialdehyde, and enhancement of manganese superoxide dismutase antioxidant capacity. Crucially, paeonol used the mitochondrial entry mechanism mediated by the translocater protein (TSPO). By blocking the oxidative stress-apoptosis cascade, downregulating Bax, preserving Bcl-2, and inhibiting cytochrome c efflux, the early/late apoptotic population was significantly reduced. This study confirmed that TSPO-mediated intra-mitochondrial antioxidant paeonol alleviates DX-induced mitochondrial dysfunction, oxidative stress, and Apoptosis in SV40-MES-13 cells.

Keywords

Apoptosis; Dexamethasone; Mitochondrial function; Oxidative stress damage; Paeonol; Translocator protein.

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