Autophagy Functions to Prevent Methylglyoxal-Induced Apoptosis in HK-2 Cells

Park, So‐Hyun; Choi, Hyun-Il; Ahn, Jiyun; Jang, Youngjin; Ha, Tae‐Youl; Seo, Hyo‐Deok; Kim, Yoon‐Sook; Lee, Dae-Hee; Jung, Chang Hwa

doi:10.1155/2020/8340695

Cited by 8 publications

(9 citation statements)

References 41 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As observed using these mouse models, renal tubular injury and deterioration of renal insufficiency are more pronounced in ATG-knockout mice after I/R than in control mice, confirming that autophagy exerts a protective effect on mouse renal I/R injury [36,37] . Moreover, the inactivation of autophagy promotes apoptosis, which suggests that increased autophagy inhibits apoptosis and plays a protective role [8,38] …”

Section: Discussionsupporting

confidence: 59%

“…Moderate levels of autophagy are currently thought to play an important role in maintaining the structure and function of tubular epithelial cells. [7][8][9] Recent research has suggested that microRNAs (miRNAs) are closely related to autophagy. [10] miRNAs are single-stranded non-coding RNAs of 19-23 nucleotides that regulate gene expression through the posttranscriptional repression of their target mRNAs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exosomal transfer of microRNA-590-3p between renal tubular epithelial cells after renal ischemia-reperfusion injury regulates autophagy by targeting TRAF6

Chen

Zhang

et al. 2022

Chinese Medical Journal

View full text Add to dashboard Cite

Background: Acute kidney injury (AKI) is a common complication in patients, especially elderly patients, who undergo cardiac surgery with cardiopulmonary bypass. Studies have indicated a protective role of autophagy in AKI. However, the mechanisms underlying the regulatory effect of autophagy in AKI among patients undergoing cardiac surgeries are poorly understood. In this study, we aimed to test the hypothesis that exosomal microRNAs (miRNAs) regulate autophagy in tubular epithelial cells after AKI. Methods: Plasma exosomal RNA was extracted from young and elderly AKI patients undergoing cardiac surgery, and the miRNAs expression during the perioperative period were analyzed using next-generation sequencing. The screened miRNAs and their target genes were subjected to gene oncology function and Kyoto Encyclopedia of Genes and Genome enrichment analyses. Renal tubular epithelial cell line (HK-2 cells) was cultured and hypoxia/reoxygenation (H/R) model was established, which is an in vitro renal ischemia/reperfusion (I/R) model. We used Western blot analysis, cell viability assay, transfection, luciferase assay to investigate the mechanisms underlying the observed increases in the levels of renal I/R injury-mediated exosomal miRNAs and their roles in regulating HK-2 cells autophagy. Results: miR-590-3p was highly enriched in the plasma exosomes of young AKI patients after cardiac surgery. Increased levels of miR-590-3p led to the increases in the expression of autophagy marker proteins, including Beclin-1 and microtubule associated protein 1 light chain 3 beta (LC3II), and prolonged the autophagic response in HK-2 cells after H/R treatment. These effects were achieved mainly via increases in the exosomal miR-590-3p levels, and the tumor necrosis factor receptor-associated factor 6 protein was shown to play a key role in I/R injury-mediated autophagy induction. Conclusion: Exosomes released from HK-2 cells after renal I/R injury regulate autophagy by transferring miR-590-3p in a paracrine manner, which suggests that increasing the miR-590-3p levels in HK-2 cell-derived exosomes may increase autophagy and protect against kidney injury after renal I/R injury.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Exosomal transfer of microRNA-590-3p between renal tubular epithelial cells after renal ischemia-reperfusion injury regulates autophagy by targeting TRAF6

Chen

Zhang

et al. 2022

Chinese Medical Journal

View full text Add to dashboard Cite

show abstract

“…MGO has been reported to decrease cell viability and induce cellular apoptosis in multiple cell types [ 45 , 46 ], including HUVECs [ 47 ]. Our present data clearly demonstrated that MGO treatment significantly reduced HUVEC viability and increased HUVEC apoptosis and that MET protected HUVECs from MGO-induced apoptosis in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo

Wang

Yang

et al. 2022

Cell Death Dis

View full text Add to dashboard Cite

Methylglyoxal (MGO) is an active metabolite of glucose and plays a prominent role in the pathogenesis of diabetic vascular complications, including endothelial cell apoptosis induced by oxidative stress. Metformin (MET), a widely prescribed antidiabetic agent, appears to reduce excessive reactive oxygen species (ROS) generation and limit cell apoptosis. However, the molecular mechanisms underlying this process are still not fully elucidated. We reported here that MET prevents MGO-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Protein expression and protein phosphorylation were investigated using western blotting, ELISA, and immunohistochemical staining, respectively. Cell viability and apoptosis were assessed by the MTT assay, TUNEL staining, and Annexin V-FITC and propidium iodide double staining. ROS generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Our results revealed that MET prevented MGO-induced HUVEC apoptosis, inhibited apoptosis-associated biochemical changes such as loss of MMP, the elevation of the Bax/Bcl-2 ratio, and activation of cleaved caspase-3, and attenuated MGO-induced mitochondrial morphological alterations in a dose-dependent manner. MET pretreatment also significantly suppressed MGO-stimulated ROS production, increased signaling through the ROS-mediated PI3K/Akt and Nrf2/HO-1 pathways, and markedly elevated the levels of its downstream antioxidants. Finally, similar results were obtained in vivo, and we demonstrated that MET prevented MGO-induced oxidative damage, apoptosis, and inflammation. As expected, MET reversed MGO-induced downregulation of Nrf2 and p-Akt. In addition, a PI3K inhibitor (LY-294002) and a Nrf2 inhibitor (ML385) observably attenuated the protective effects of MET on MGO-induced apoptosis and ROS generation by inhibiting the Nrf2/HO-1 pathways, while a ROS scavenger (NAC) and a permeability transition pores inhibitor (CsA) completely reversed these effects. Collectively, these findings broaden our understanding of the mechanism by which MET regulates apoptosis induced by MGO under oxidative stress conditions, with important implications regarding the potential application of MET for the treatment of diabetic vascular complications.

show abstract

“…Then, the accumulated MGO further induces oxidative stress, apoptosis and genotoxicity, which plays an important pathophysiological role in the toxic injury of diabetic complications [14–16] . Studies have shown that MGO caused oxidative stress and inflammation in kidney epithelial cell lines (HK‐2 cells), induced apoptosis and autophagy and aggravated the development of diabetic nephropathy [17,18] . In addition, MGO can react with protein, produce advanced glycosylation end products (AGEs).…”

Section: Introductionmentioning

confidence: 99%

Potential Mechanisms of Methylglyoxal‐Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis

Liú

Cheng

Tang

et al. 2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

Methylglyoxal (MGO) is a reactive carbonyl species that can cause cellular damage and is closely related to kidney disease, especially diabetic nephropathy. The toxic effect of MGO (0.5, 1, and 2 mM) on human embryonic kidney (HEK293) cells and its underlying mechanisms were explored in this study. Cell viability, apoptosis and the signaling pathways were measured with MTT, fluorescent staining and western blot experiments, the results showed that MGO could induce oxidative stress and cell inflammation, the level of reactive oxygen species (ROS) increased, and p38MAPK, JNK and NF‐κB signaling pathways were activated. Meanwhile, MGO also induced DNA damage. The expression of DNA oxidative damage marker 8‐hydroxy‐2’‐deoxyguanosine (8‐OHdG) increased, the expression of double‐strand break marker γH2AX increased significantly, and ATM/Chk2/p53 DNA damage response signaling pathway was activated. Furthermore, the expression of the receptor for advanced glycation end products (RAGE) also increased. Finally, mitochondrial membrane potential (MMP) decreased, fluorescence intensity of Hoechst33258 increased, and the protein expression ratio of Bax/Bcl‐2 increased significantly after the treatment of MGO. These results demonstrated that MGO might induce HEK293 cells damage by regulating oxidative stress, inflammation, DNA damage, and cell apoptosis, which revealed the specific mechanisms of MGO‐induced damage to HEK293 cells.

show abstract

Autophagy Functions to Prevent Methylglyoxal-Induced Apoptosis in HK-2 Cells

Cited by 8 publications

References 41 publications

Exosomal transfer of microRNA-590-3p between renal tubular epithelial cells after renal ischemia-reperfusion injury regulates autophagy by targeting TRAF6

Exosomal transfer of microRNA-590-3p between renal tubular epithelial cells after renal ischemia-reperfusion injury regulates autophagy by targeting TRAF6

Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo

Potential Mechanisms of Methylglyoxal‐Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis

Contact Info

Product

Resources

About