Glyoxalase System in the Progression of Skin Aging and Skin Malignancies

Yumnam, Silvia; Subedi, Lalita; Kim, Sun Yeou

doi:10.3390/ijms22010310

Cited by 27 publications

(19 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MGO is a highly reactive dicarbonyl metabolite of glucose known to induce cellular apoptosis, oxidative stress, inflammation, and AGE formation in ECs [40,41]. The accumulation of MGO has been associated with organ dysfunction contributing to the pathogenesis of diabetes and vascular complications [42,43]. MET appears to reduce excessive ROS generation and cell apoptosis [44].…”

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

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

show abstract

“…Cetuximab inhibits the growth of TNBC tumors by blocking the ligand-induced phosphorylation of EGFR. Lapatinib and gefitinib are EGFR-TKIs that have also shown anti-proliferative activity in studies [ 20 , 22 , 23 ]. Investigations of PI3K, MEK1/2, Akt, and small interfering RNA are also molecules/pathways as shown in Figure 3 .…”

Section: Targets Of Tnbc Under Active Clinical Evaluationmentioning

confidence: 99%

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

Singh

Yadav

2021

Biomedicines

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.

show abstract

“…Cutaneous melanoma, an aggressive malignant tumor with increasing incidence, accounts for more than 80% of all skin cancer deaths ( Chen et al, 2019 ; Yumnam et al, 2020 ). Globally, approximately 232,100 of cutaneous melanoma are newly diagnosed, and 55,500 patients die each year ( Schadendorf et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

A Ferroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Cutaneous Melanoma

Chen

2021

Front. Genet.

View full text Add to dashboard Cite

BackgroundCutaneous melanoma is a common but aggressive tumor. Ferroptosis is a recently discovered cell death with important roles in tumor biology. Nevertheless, the prognostic power of ferroptosis-linked genes remained unclear in cutaneous melanoma.MethodsCutaneous melanoma patients of TCGA (The Cancer Genome Atlas) were taken as the training cohort while GSE65904 and GSE22153 as the validation cohorts. Multifactor Cox regression model was used to build a prognostic model, and the performance of the model was assessed. Functional enrichment and immune infiltration analysis were used to clarify the mechanisms.ResultsA five ferroptosis-linked gene predictive model was developed. ALOX5 and GCH1 were illustrated as independent predictive factors. Functional assessment showed enriched immune-linked cascades. Immune infiltrating analysis exhibited the distinct immune microenvironment.ConclusionHerein, a novel ferroptosis-related gene prognostic model was built in cutaneous melanoma. This model could be used for prognostic prediction, and maybe helpful for the targeted and immunotherapies.

show abstract

Glyoxalase System in the Progression of Skin Aging and Skin Malignancies

Cited by 27 publications

References 62 publications

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

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

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

A Ferroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Cutaneous Melanoma

Contact Info

Product

Resources

About