The Hallmarks of Aging

Cell, Journal Year: 2013, Volume and Issue: 153(6), P. 1194 - 1217

Published: June 1, 2013

Language: Английский

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mTOR Signaling in Growth, Metabolism, and Disease

Cell, Journal Year: 2017, Volume and Issue: 168(6), P. 960 - 976

Published: March 1, 2017

Language: Английский

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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Autophagy, Journal Year: 2016, Volume and Issue: 12(1), P. 1 - 222

Published: Jan. 2, 2016

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, on this topic has continued to accelerate, and many new scientists have entered field. Our knowledge base relevant technologies also been expanding. Accordingly, it is important update these monitoring autophagy different organisms. Various reviews described range assays that used purpose. Nevertheless, there continues be confusion regarding acceptable methods measure autophagy, especially multicellular eukaryotes. For example, a key point needs emphasized difference between measurements monitor numbers or volume autophagic elements (e.g., autophagosomes autolysosomes) at any stage process versus those flux through pathway (i.e., complete including amount rate cargo sequestered degraded). particular, block macroautophagy results autophagosome accumulation must differentiated from stimuli increase activity, defined as increased induction coupled with delivery to, degradation within, lysosomes (in most higher eukaryotes some protists such Dictyostelium) vacuole plants fungi). other words, investigators field understand appearance more does not necessarily equate fact, cases, accumulate because trafficking without concomitant change biogenesis, whereas an autolysosomes may reflect reduction degradative activity. It worth emphasizing here lysosomal digestion evaluating its competence crucial part evaluation flux, autophagy. Here, present selection interpretation use by who aim examine related processes, well reviewers need provide realistic reasonable critiques papers are focused processes. These meant formulaic rules, appropriate depend question being asked system used. addition, emphasize no individual assay guaranteed one every situation, strongly recommend multiple Along lines, potential pleiotropic effects due blocking genetic manipulation, imperative target gene knockout RNA interference than autophagy-related protein. Atg proteins, groups involved cellular pathways implying all proteins can specific marker process. guidelines, consider various assessing what information can, cannot, obtained them. Finally, discussing merits limits particular assays, hope encourage technical innovation

Language: Английский

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Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

Cellular Physiology and Biochemistry, Journal Year: 2017, Volume and Issue: 42(5), P. 1725 - 1738

Published: Jan. 1, 2017

To investigate whether oxidative stress modulates vascular endothelial growth factor (VEGF)-A and VEGF-C expression polarized secretion in a human retinal pigment epithelium cell line (ARPE-19).Long-term culture of ARPE-19 cells Dulbecco's modified Eagle medium (DMEM)/F12 containing 1% fetal bovine serum (FBS) on transwell filters (12 mm or 6 mm, pore size 0.4 microm) was performed to produce (RPE) monolayers. The integrity monolayer established by measurement transepithelial resistance (TER) presence tight junctions assessed zonula occludens (ZO-1) occludin apical Na/K ATPase localization. Paracellular permeability studied using radiolabeled mannitol. Confluent were treated with tertiary butyl hydrogen peroxide (tBH) for varying durations (0-5 h) doses (50-200 microM). VEGF-A -C evaluated western blot quantitative RT-PCR, while the basolateral surfaces quantitated ELISA.Polarity verified localization junction proteins, ZO-1 its binding partner confocal microscopy as well Na,K-ATPase at surface. TER confluent averaged 48.7+/-2.1 Omega. cm(2) tBH treatment did not alter significantly (46.9+/-1.9 cm(2); p>0.05 versus controls) expression. Whole mRNA nonpolarized increased 5 h both increase significant (p<0.05 vs controls). A similar, maximal also observed cellular protein levels. ARPE showed an exposure. levels higher monolayers stimulated domains. 150 microM function time (1-5 increases from 410 2080 pg/10(6) 290 1680 pattern similar. dose-dependent range 50-200 tended be than secretion.Our data show that RPE upregulates C. side Given role VEGF choroidal neovascularization, these may value understanding pathogenic mechanisms designing antiangiogenic therapies.

Language: Английский

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Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression

Neurosignals, Journal Year: 2012, Volume and Issue: 21(1-2), P. 28 - 41

Published: March 28, 2012

Despite an alarming increase in the burden of obesity worldwide, body adiposity seems to be a regulated physiological variable. Regulation occurs through classical endocrine feedback loop, which pancreatic beta-cell-derived hormone insulin and adipocyte-derived leptin signal status energy stores hypothalamus. Recent advances our understanding transduction mechanisms used by hypothalamus modulate neuronal firing suggest that intracellular cross-talk at several levels is potentially important determinant weight. These pathways are thus attractive target for pharmacological intervention treatment obesity.

Language: Английский

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The ground state of embryonic stem cell self-renewal

Nature, Journal Year: 2008, Volume and Issue: 453(7194), P. 519 - 523

Published: May 1, 2008

Language: Английский

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Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets

Cell, Journal Year: 2009, Volume and Issue: 136(4), P. 731 - 745

Published: Feb. 1, 2009

Language: Английский

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AKT/PKB Signaling: Navigating the Network

Cell, Journal Year: 2017, Volume and Issue: 169(3), P. 381 - 405

Published: April 1, 2017

Language: Английский

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AMPK: guardian of metabolism and mitochondrial homeostasis

Nature Reviews Molecular Cell Biology, Journal Year: 2017, Volume and Issue: 19(2), P. 121 - 135

Published: Oct. 4, 2017

Language: Английский

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mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt

Cancer Research, Journal Year: 2006, Volume and Issue: 66(3), P. 1500 - 1508

Published: Feb. 1, 2006

Abstract Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent loss in substrate-1 expression leading to feedback down-regulation signaling through pathway. In model systems, tumors exhibiting mutational activation phosphoinositide-3-kinase/Akt kinase, a common event cancers, are hypersensitive mTOR inhibitors, rapamycin. Despite activity patients, inhibitors exhibit more modest antitumor activity. We now show that inhibition induces abrogates pathway, resulting Akt both cancer cell lines patient treated with rapamycin derivative, RAD001. IGF-I prevents rapamycin-induced sensitizes tumor cells mTOR. contrast, reverses antiproliferative serum-free medium. The data suggest tyrosine kinase is frequent constitutive activation. Reversal this loop by may attenuate its therapeutic effects, whereas combination therapy ablates function have improved (Cancer Res 2006; 66(3): 1500-8)

Language: Английский

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