ROS Production and ERK Activity Are Involved in the Effects of d-β-Hydroxybutyrate and Metformin in a Glucose Deficient Condition

Lamichhane, Santosh; Bastola, Tonking; Pariyar, Ramesh; Lee, Eun-Sol; Lee, Ho-Sub; Lee, Dong Hoon; Seo, Jooyeok

doi:10.3390/ijms18030674

Cited by 20 publications

(15 citation statements)

References 47 publications

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“…ROS can initiate apoptosis of podocytes, induce podocytes to exfoliate from basement membrane, and decrease the number of podocytes in glomeruli . Metformin can not only inhibit the production of NADPH oxidase and AGEs, thus reducing ROS content in podocytes cultured in vitro, but also reduce oxidative stress by increasing the activity of peroxidase and the production of SOD and GSH . In this study, the BG, serum uric acid, BUN and UACR decreased significantly in MET ( P < .01) treatment group compared with that of DM group, and the decreased levels were metformin‐dependent.…”

Section: Discussionmentioning

confidence: 48%

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Liu

et al. 2020

Clin Exp Pharma Physio

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Diabetic nephropathy (DN) is the major microvascular complication of diabetes mellitus and the most important cause of end‐stage renal disease worldwide. Metformin is the preferred oral hypoglycaemic drug for type 2 diabetes mellitus (T2DM). Recent studies have shown that besides lowering blood glucose, metformin also has protective effects on renal function, but its mechanism is not clear. In this study, we established a diabetic rat model by high‐fat feeding combined with intraperitoneal injection of streptozotocin. Their changes of renal function, oxidative stress, histopathology and structure, and autophagy were observed after 8 weeks of metformin treatment at different dose. Sirt1 inhibitor EX527 and metformin were used to observe whether the protective effect of metformin on DN kidney was achieved through the Sirt1/FoxO1 autophagic signalling pathway. The results showed that metformin could protect renal function by up‐regulating autophagy level, alleviating oxidative stress level of renal tissue and pathological and structural changes of glomeruli, and inhibiting the expression of extracellular matrix. Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis. So metformin could alleviate renal injury in diabetic rats, which may be achieved by regulating Sirt1/FoxO1 autophagic signalling pathway and inducing renal autophagy.

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Section: Discussionmentioning

confidence: 48%

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Liu

et al. 2020

Clin Exp Pharma Physio

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“… 10 , 11 The primary molecular role of Met is inhibiting mitochondrial respiratory complex I, namely, reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase, which could reduce cellular synthesis of ATP and induce reactive oxygen species (ROS) imbalance. 12 In fact, some studies have indicated that Met could increase the level of ROS in lung cancer and breast cancer, 13 , 14 but no report has shown the association of biguanides and ROS in glioma cells.…”

Section: Introductionmentioning

confidence: 99%

Phenformin and metformin inhibit growth and migration of LN229 glioma cells in vitro and in vivo

Wang¹,

Meng²,

Zhang³

et al. 2018

OTT

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BackgroundMalignant glioma is refractory to conventional treatment, highlighting a need to develop novel efficacious therapies. Biguanides, a class of oral antidiabetic drug, have been thought to inhibit proliferation and metastasis in a variety of cancers.PurposeThe objective of this study was to investigate the affections of biguanides, phenformin (Phen) and metformin (Met), on growth and migration of glioma cells LN229 in vitro and in vivo.MethodsGlioma cells LN229 were treated with Phen or Met, then cell proliferation and death were evaluated by MTT assay and PI stain, and cell cycle were evaluated using flow cytometric analysis, meantime wound healing assay and transwell migration assay were performed to detect cell migration ability. In addition, LN229 were injected in thigh of nude mice, and the mice were treated with Phen or Met to detect the effect of Phen and Met in vivo.ResultsPhen and Met could significantly inhibit cell growth through inhibiting cell proliferation, promoting cell death and disturbing cell cycle, and these drugs also could inhibit cell colony formation in glioma cells LN229 in vitro. Meanwhile, both Phen and Met could significantly inhibit cell migration of LN229 in vitro, through effecting the expression of E-cadherin and Vimentin. In addition, both Phen and Met inhibited the growth and migration of LN229 in a tumor xenograft model. Furthermore, Phen and Met were associated with the increased level of ROS of cell mitochondrial, and ROS inhibitor NAC could significantly rescue the cell death induced by Phen and Met.ConclusionPhen and Met displayed powerful antitumor effects of LN229, and our findings powerfully suggest the possibility of Phen and Met being used as an adjuvant agent in the treatment of glioma patients.

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“…In case of ERK, it was reported that MPP + increased α-synuclein expression through ROS production and the increased α-synuclein expression inactivated ERK, thereby increasing caspase 3 activation [ 71 ]. We previously reported that glucose deficiency increased ROS production and decreased ERK phosphorylation in SH-SY5Y cells [ 72 ]. Interestingly, ROS inhibitor clearly recovered ERK phosphorylation decreased by glucose deficiency, suggesting ROS-induced downregulation in ERK phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Sulfuretin Attenuates MPP+-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways

Pariyar

Lamichhane

Jung

et al. 2017

IJMS

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Parkinson’s disease (PD) is the second most common neurodegenerative disease. It is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress and mitochondrial dysfunction contribute to the loss of dopaminergic neurons in PD. Sulfuretin is a potent antioxidant that is reported to be beneficial in the treatment of neurodegenerative diseases. In this study, we examined the protective effect of sulfuretin against 1-methyl-4-phenyl pyridinium (MPP+)-induced cell model of PD in SH-SY5Y cells and the underlying molecular mechanisms. Sulfuretin significantly decreased MPP+-induced apoptotic cell death, accompanied by a reduction in caspase 3 activity and polyADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated MPP+-induced production of intracellular reactive oxygen species (ROS) and disruption of mitochondrial membrane potential (MMP). Consistently, sulfuretin decreased p53 expression and the Bax/Bcl-2 ratio. Moreover, sulfuretin significantly increased the phosphorylation of Akt, GSK3β, and ERK. Pharmacological inhibitors of PI3K/Akt and ERK abolished the cytoprotective effects of sulfuretin against MPP+. An inhibitor of GSK3β mimicked sulfuretin-induced protection against MPP+. Taken together, these results suggest that sulfuretin significantly attenuates MPP+-induced neurotoxicity through Akt/GSK3β and ERK signaling pathways in SH-SY5Y cells. Our findings suggest that sulfuretin might be one of the potential candidates for the treatment of PD.

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ROS Production and ERK Activity Are Involved in the Effects of d-β-Hydroxybutyrate and Metformin in a Glucose Deficient Condition

Cited by 20 publications

References 47 publications

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Phenformin and metformin inhibit growth and migration of LN229 glioma cells in vitro and in vivo

Sulfuretin Attenuates MPP+-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways

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