A pioneer in the field of autophagy microscopy

Kovács, Attila; Klionsky, Daniel J.

doi:10.4161/auto.26613

Cited by 2 publications

(2 citation statements)

References 53 publications

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“…Ahr -/-MLFs was indeed associated with autophagy, we assessed transmission electron micrographs (TEMs) for the presence of autophagosomes, a technique/read-out considered to be the gold standard for validating autophagy (42). However, there was a distinct absence of an accumulation of autophagosomes in the Ahr -/-MLFs, although some autophagosomes (black arrowheads) were observed (Fig.…”

Section: Ahr Deficiency Results In Er Stress-in An Attempt To Determi...mentioning

confidence: 99%

The aryl hydrocarbon receptor reduces LC3II expression and controls endoplasmic reticulum stress

Guerrina

Aloufi

Shi

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose physiological function is poorly understood. The AhR is highly expressed in barrier organs such as the skin, intestine and lung. The lungs are continuously exposed to environmental pollutants such as cigarette smoke (CS) that can induce cell death mechanisms such as apoptosis, autophagy and endoplasmic reticulum (ER) stress. CS also contains toxicants that are AhR ligands. We have previously shown that the AhR protects against apoptosis, but whether the AhR also protects against autophagy or ER stress is not known. Using cigarette smoke extract (CSE) as our in vitro surrogate of environmental tobacco exposure, we first assessed the conversion of LC3I to LC3II, a classic feature of both autophagic and ER stress-mediated cell death pathways. LC3II was elevated in CSE-exposed lung structural cells (mouse lung fibroblasts [MLFs], MLE12 and A549 cells) when AhR was absent. However, this heightened LC3II expression could not be explained by increased expression of key autophagy genes (Gabarapl1, Becn1, Map1lc3b), upregulation of upstream autophagic machinery (Atg5-12, Atg3) or by impaired autophagic flux, suggesting that LC3II may be autophagy-independent. This was further supported by the absence of autophagosomes in Ahr-/- lung cells. However, Ahr-/- lung cells had widespread ER-dilation, elevated expression of the ER stress markers CHOP and GADD34 and an accumulation of ubiquitinated proteins. These findings collectively illustrate a novel role for the AhR in attenuating ER stress by a mechanism that may be autophagy-independent.

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Section: Ahr Deficiency Results In Er Stress-in An Attempt To Determi...mentioning

confidence: 99%

The aryl hydrocarbon receptor reduces LC3II expression and controls endoplasmic reticulum stress

Guerrina

Aloufi

Shi

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…As the most reliable method and gold standard for detecting phagocytosis (15), TEM was used to clearly observe the independent bilayer membrane structure of autophagosomes and various autophagic morphological changes at x10,000 magnification. Autophagosomes in the control group and the Ang II group were observed by TEM (JEOL, Ltd.).…”

Section: Observation Of Autophagosomes By Transmission Electron Microscopy (Tem)mentioning

confidence: 99%

MicroRNA and mRNA analysis of angiotensin II‑induced renal artery endothelial cell dysfunction

Liu

Jiang

et al. 2020

Exp Ther Med

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Continuous activation of angiotensin II (Ang II) induces renal vascular endothelial dysfunction, inflammation and oxidative stress, all of which may contribute to renal damage. MicroRNAs (miRs/miRNAs) play a crucial regulatory role in the pathogenesis of hypertensive nephropathy (HN). The present study aimed to assess the differential expression profiles of potential candidate genes involved in Ang II-induced rat renal artery endothelial cell (RRAEC) dysfunction and explore their possible functions. In the present study, the changes in energy metabolism and autophagy function in RRAECs were evaluated using the Seahorse XF Glycolysis Stress Test and dansylcadaverine/transmission electron microscopy following exposure to Ang II. Subsequently, mRNA-miRNA sequencing experiments were performed to determine the differential expression profiles of mRNAs and miRNAs. Integrated bioinformatics analysis was applied to further explore the molecular mechanisms of Ang II on endothelial injury induced by Ang II. The present data supported the notion that Ang II upregulated glycolysis levels and promoted autophagy activation in RRAECs. The sequencing data demonstrated that 443 mRNAs and 58 miRNAs were differentially expressed (DE) in response to Ang II exposure, where 66 mRNAs and 55 miRNAs were upregulated, while 377 mRNAs and 3 miRNAs were downregulated (fold change >1.5 or <0.67; P<0.05). Functional analysis indicated that DE mRNA and DE miRNA target genes were mainly associated with cell metabolism (metabolic pathways), differentiation (Th1 and Th2 cell differentiation), autophagy (autophagy-animal and autophagy-other) and repair (RNA-repair). To the best of the authors' knowledge, this is the first report on mRNA-miRNA integrated profiles of Ang II-induced RRAECs. The present results provided evidence suggesting that the miRNA-mediated effect on the 'mTOR signaling pathway' might play a role in Ang II-induced RRAEC injury by driving glycolysis and autophagy activation. Targeting miRNAs and their associated pathways may provide valuable insight into the clinical management of HN and may improve patient outcome.

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A pioneer in the field of autophagy microscopy

Cited by 2 publications

References 53 publications

The aryl hydrocarbon receptor reduces LC3II expression and controls endoplasmic reticulum stress

The aryl hydrocarbon receptor reduces LC3II expression and controls endoplasmic reticulum stress

MicroRNA and mRNA analysis of angiotensin II‑induced renal artery endothelial cell dysfunction

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