Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation

Immunity, Journal Year: 2021, Volume and Issue: 54(7), P. 1463 - 1477.e11

Published: June 10, 2021

Language: Английский

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Distinct Types of Cell Death and the Implication in Diabetic Cardiomyopathy

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Feb. 6, 2020

Diabetic cardiomyopathy (DCM) is a chronic complication of diabetes mellitus, characterized by abnormalities myocardial structure and function. The researches on the models type 1 2 as well application genetic engineering technology help to understand molecular mechanism DCM. DCM has multiple hallmarks, including hyperglycemia, insulin resistance, increased free radical production, lipid peroxidation, mitochondrial dysfunction, endothelial dysfunction cell death. Essentially, death considered be terminal pathway cardiomyocytes during Morphologically, can classified into four different forms: apoptosis, autophagy, necrosis entosis. Apoptosis, I death, fastest form mainly occurs depending caspase proteolytic cascade. Autophagy, II degradation process remove damaged proteins, dysfunctional organelles commences formation autophagosome. Necrosis III which contains great diversity processes, such necroptosis pyroptosis. Entosis IV displaying "cell-in-cell" cytological features requires engulfing cells execute. There are also some other types ferroptosis, parthanatos, netotic lysosomal dependent alkaliptosis or oxeiptosis, possibly involved in Drugs compounds targeting signals have been used clinic experiment treat This review briefly summarizes mechanisms implications DCM, beneficial improve understanding may propose novel ideal strategies future.

Language: Английский

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NLRP3 inflammasome, an immune‐inflammatory target in pathogenesis and treatment of cardiovascular diseases

Clinical and Translational Medicine, Journal Year: 2020, Volume and Issue: 10(1), P. 91 - 106

Published: March 1, 2020

Abstract Inflammation is an important process involved in several cardiovascular diseases (CVDs), and nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome a vital player innate immunity inflammation. In this review, we aim to provide comprehensive summary of the current knowledge on role involvement NLRP3 pathogenesis treatment CVDs. functions as molecular platform, triggers activation caspase‐1 cleavage pro‐IL‐1β, pro‐IL‐18, gasdermin D (GSDMD). Cleaved NT‐GSDMD forms pores cell membrane initiates pyroptosis, inducing death release many intracellular pro‐inflammatory molecules. triggered via inter‐related pathways downstream K + efflux, lysosomal disruption, mitochondrial dysfunction. addition, Golgi apparatus noncoding RNAs are gradually being recognized play roles activation. Many investigations have revealed association between CVDs, including atherosclerosis, ischemia/reperfusion (I/R) injury heart failure induced by pressure overload or cardiomyopathy. Some existing medications, orthodox natural medicines, used for CVD been newly discovered act inflammasome. pathway components such NLRP3, caspase‐1, IL‐1β may be considered novel therapeutic targets Thus, key molecule further research focused development inflammasome‐based targeted therapies CVDs clinical evaluation these essential.

Language: Английский

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A new research hot spot: The role of NLRP3 inflammasome activation, a key step in pyroptosis, in diabetes and diabetic complications

Life Sciences, Journal Year: 2019, Volume and Issue: 240, P. 117138 - 117138

Published: Dec. 3, 2019

Language: Английский

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SARS-CoV-2 viroporin encoded by ORF3a triggers the NLRP3 inflammatory pathway

Virology, Journal Year: 2022, Volume and Issue: 568, P. 13 - 22

Published: Jan. 17, 2022

Language: Английский

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Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 68, P. 101338 - 101338

Published: April 7, 2021

Language: Английский

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The effects of metformin on autophagy

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 137, P. 111286 - 111286

Published: Jan. 30, 2021

Metformin is the first-line option for treating newly diagnosed diabetic patients and also involved in other pharmacological actions, including antitumor effect, anti-aging polycystic ovarian syndrome prevention, cardiovascular action, neuroprotective etc. However, mechanisms of metformin actions were not fully illuminated. Recently, increasing researches showed that autophagy a vital medium playing actions. Nevertheless, results on effects inconsistent. Apart from few clinical evidences, more data focused kinds no-clinical models. First, many studies could induce via number signaling pathways, AMPK-related pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3β, TRIB3. Secondly, some process inhibiting autophagy, such as (AMPK/NF-κB undetermined pathways), Hedgehog, miR-570-3p, miR-142-3p, MiR-3127-5p. Thirdly, two types PI3K/AKT/mTOR endoplasmic reticulum (ER) stress bidirectionally impact effectiveness autophagy. Finally, multiple signal reviewed collectively terms affecting The combining its discussed. It would help better apply to treat diseases term mediating

Language: Английский

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Mitochondrial dysfunction as a driver of NLRP3 inflammasome activation and its modulation through mitophagy for potential therapeutics

The International Journal of Biochemistry & Cell Biology, Journal Year: 2021, Volume and Issue: 136, P. 106013 - 106013

Published: May 19, 2021

Language: Английский

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Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications

Pharmacological Research, Journal Year: 2022, Volume and Issue: 177, P. 106114 - 106114

Published: Feb. 3, 2022

Language: Английский

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The advanced glycation end-products (AGEs)/ROS/NLRP3 inflammasome axis contributes to delayed diabetic corneal wound healing and nerve regeneration

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(2), P. 809 - 825

Published: Jan. 1, 2022

Diabetic keratopathy (DK) is an important diabetic complication at the ocular surface.Chronic low-grade inflammation mediated by NLRP3 inflammasome promotes pathogenesis of diabetes and its complications.However, effect on DK remains elusive.Wild-type (WT) Nlrp3 knockout (KO) C57BL/6 mice were used to establish a type I model intraperitoneal injection streptozotocin.The corneal wound healing never regeneration was examined epithelial abrasion model.Western blot, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) pharmacological treatment performed investigate regulatory mechanism advanced glycation end products (AGEs) activation in vivo.The cultured mouse cells (TKE2) evaluate AGEs vitro.We revealed that inflammasome-mediated pyroptosis contributed pathogenesis.Under physiological conditions, required for nerve regeneration.However, under scenario, sustained resulted postponed impaired regeneration.Mechanistically, accumulated promoted hyperactivation through ROS production.Moreover, genetically pharmacologically blocking AGEs/ROS/NLRP3 axis significantly expedited closure regeneration.Our results AGEs-induced delayed regeneration, which further highlighted as promising target treatment.

Language: Английский

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