Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2

In this study, we exposed wild-type (WT) and AMPKα2−/− mice to PM2.5 every other day via intratracheal instillation for 4 weeks. After PM2.5 exposure, the AMPKα2−/− mice developed more severe lung injury and cardiac dysfunction than were developed in the WT mice; however the administration of metformin was effective in attenuating PM2.5-induced lung injury and cardiac dysfunction in both the WT and AMPKα2−/− mice. In the PM2.5-exposed mice, metformin treatment resulted in reduced systemic and pulmonary inflammation, preserved left ventricular ejection fraction, suppressed induction of pulmonary and myocardial fibrosis and oxidative stress, and increased levels of mitochondrial antioxidant enzymes. Moreover, pretreatment with metformin significantly attenuated PM2.5-induced cell death and oxidative stress in control and AMPKα2-depleted BEAS-2B and H9C2 cells, and was associated with preserved expression of mitochondrial antioxidant enzymes. These data support the notion that metformin protects against PM2.5-induced adverse health effects through a pathway that appears independent of AMPKα2. Our findings suggest that metformin may also be a novel drug for therapies that treat air pollution associated disease.Graphical abstract
Source: Redox Biology - Category: Biology Source Type: research

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ConclusionGP-17 inhibits I/R-induced mitochondrial injuryby delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.
Source: Journal of Ginseng Research - Category: Complementary Medicine Source Type: research
ConclusionIn conclusion PKR activation plays an important role in the pathogenesis of vascular inflammation and remodelling, and therapeutically targeting PKR could be an effective approach to treat the abnormalities associated with vascular complications.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Mutations in lysosomal export protein NPC1 have unexpectedly widespread consequences for the life of the cell. These are summarized and integrated in the present Review. The diverse approaches to therapy taken so far are surveyed. AbstractNiemann –Pick type C disease (NPCD) was first described in 1914 and affects approximately 1 in 150 000 live births. It is characterized clinically by diverse symptoms affecting liver, spleen, motor control, and brain; premature death invariably results. Its molecular origins were traced, as late as 1997, to a protein of late endosomes and lysosomes which was named NPC1. Mutatio...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Review Source Type: research
Matthew O'Conner presented at Undoing Aging earlier this year on the startup biotech company Underdog Pharmaceuticals. The company is spinning out of the SENS Research Foundation (SRF), based on research conducted by the scientific team there in recent years. The company is focused on a class of molecule known cyclodextrins, and have candidates capable of efficiently binding and sequestering 7-ketocholesterol. This form of oxidized cholesterol is of great importance to the progression of atherosclerosis, and possibly other age-related conditions as well. In the case of atherosclerosis, the presence of oxidized cholesterols...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
Publication date: Available online 14 November 2019Source: Pharmacological ResearchAuthor(s): Thomas Datzmann, Andrea Hoffmann, Oscar McCook, Tamara Merz, Ulrich Wachter, Jonathan Preuss, Sabine Vettorazzi, Enrico Calzia, Michael Gröger, Fabian Kohn, Andreas Schmid, Nicole Denoix, Peter Radermacher, Martin WeplerAbstractControversial data are available on hydrogen sulfide (H2S) during hemorrhage and resuscitation, depending on timing, dosing, mode of application, and the H2S donor used. Sodium thiosulfate (Na2S2O3) is a recognized drug devoid of major side effects, which attenuated murine acute lung injury and cerebra...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Environmental Science&TechnologyDOI: 10.1021/acs.est.9b05131
Source: Environmental Science and Technology - Category: Environmental Health Authors: Source Type: research
Cell Death &Disease, Published online: 14 November 2019; doi:10.1038/s41419-019-2091-2Mitochondrial damage by α-synuclein causes cell death in human dopaminergic neurons
Source: Cell death and disease - Category: Internal Medicine Authors: Source Type: research
In conclusion, Vilda purveyed significant anti-Huntington effect which may be mediated, at least in part, via activation of GLP-1/PI3K/Akt pathway in 3NP rat model.
Source: Neurotherapeutics - Category: Neurology Source Type: research
Throughout the animal kingdom, mitochondria are the only organelles that retain their own genome and the transcription and translation machineries that are all essential for energy harvesting. Mitochondria have developed a complex communication network, allowing them to stay in tune with cellular needs and nuclear transcriptional programs and to alleviate mitochondrial dysfunction. Here, we review recent findings on the wide array of mechanisms that contribute to these mitocellular communication networks, spanning from well-studied messenger molecules to mitonuclear genetic interactions. Based on these observations and dev...
Source: ScienceNOW - Category: Science Authors: Tags: Cell Biology special/review Source Type: news
Publication date: Available online 12 November 2019Source: MicronAuthor(s): Andrezza Raposo Borges de Melo, Taciana Mirely Maciel Higino, Aline Dulce Pitt da Rocha Oliveira, Adriana Fontes, Diego César Nunes da Silva, Maria Carolina Accioly Brelaz de Castro, José Arimatéia Dantas Lopes, Regina Celia Bressan Queiroz de FigueiredoAbstractChagas disease, caused by the protozoan Trypanosoma cruzi, is considered a public health problem. The current chemotherapy for this illness causes serious side effects and its use in the chronic phase of the disease is still controversial. In this sense, the investigatio...
Source: Micron - Category: Biology Source Type: research
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