Autophagy

Hale, Amber; Ledbetter, Dan; Gawriluk, Thomas R.; Rucker, Edmund B.

doi:10.4161/auto.24273

Cited by 268 publications

(140 citation statements)

References 236 publications

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“…The structures enclosed by double membranes and containing unwanted or damaged cellular organelles, and partially digested material were considered as autophagic vacuoles (av, Fig. 1B) (Tu et al, 2011; Hale et al, 2013; Galluzzi & Kroemer, 2015). …”

Section: Methodsmentioning

confidence: 99%

Morphometric analysis of a triple negative breast cancer cell line in hydrogel and monolayer culture environments

Jogalekar

Serrano

2018

PeerJ

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Triple negative breast cancer (TNBC) is a belligerent carcinoma that is unresponsive to targeted receptor therapies. Development of new treatment strategies would benefit from an expanded repertoire of in vitro cell culture systems, such as those that support tridimensional growth in the presence of hydrogel scaffolds. To this end, we established protocols for maintenance of the TNBC cell line HCC70 in monolayer culture and in a commercially available basement membrane matrix hydrogel. We evaluated the general morphology of cells grown in both conditions with light microscopy, and examined their subcellular organization using transmission electron microscopy (TEM). Phase contrast and confocal microscopy showed the prevalence of irregularly shaped flattened cells in monolayer cultures, while cells maintained in hydrogel organized into multi-layered spheroids. A quantitative ultrastructural analysis comparing cells from the two culture conditions revealed that cells that formed spheroids comprised a greater number of mitochondria, autophagic vacuoles and intercellular junctions than their monolayer counterparts, within the equivalent area of sampled tissue. These observations suggest that triple negative breast cancer cells in culture can alter their organelle content, as well as their morphology, in response to their microenvironment. Methods presented here may be useful for those who intend to image cell cultures with TEM, and for investigators who seek to implement diverse in vitro models in the search for therapeutic molecular targets for TNBC.

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Section: Methodsmentioning

confidence: 99%

Morphometric analysis of a triple negative breast cancer cell line in hydrogel and monolayer culture environments

Jogalekar

Serrano

2018

PeerJ

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“…To form a mature autophagosome, autophagy proceeds in successive stages, which include induction, nucleation, expansion and maturation (Wang et al 2010, Hale et al 2013. Autophagy process is regulated by a system of autophagy-related gene (ATG) products (Fig.…”

Section: Overview Of Autophagymentioning

confidence: 99%

“…Following the combination of ATG3 (E2-like enzyme), the ATG16L1 complex (E3-ligase), ATG7, and LC3 are then conjugated to PE to produce LC3-PE (also called LC3-II). LC3-II specifically localizes to the autophagosomal membranes and so it is suited to serving as an autophagy-specific marker (Dirks-Naylor 2013, Hale et al 2013, Jia & Sowers 2015.…”

Section: Expansion Of Autophagymentioning

confidence: 99%

The role of autophagy in angiotensin II-induced pathological cardiac hypertrophy

Zhou

Han

2016

Journal of Molecular Endocrinology

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Pathological cardiac hypertrophy is associated with nearly all forms of heart failure. It develops in response to disorders such as coronary artery disease, hypertension and myocardial infarction. Angiotensin II (Ang II) has direct effects on the myocardium and promotes hypertension. Chronic elevation of Ang II can lead to pathological cardiac hypertrophy and cardiac failure. Autophagy is an important process in the pathogenesis of cardiovascular diseases. Under physiological conditions, autophagy is an essential homeostatic mechanism to maintain the global cardiac structure function by ridding damaged cells or unwanted macromolecules and organelles. Dysregulation of autophagy may play an important role in Ang II-induced cardiac hypertrophy although conflicting reports on the effects of Ang II on autophagy and cardiac hypertrophy exist. Some studies showed that autophagy activation attenuated Ang II-induced cardiac dysfunction. Others suggested that inhibition of the Ang II induced autophagy should be protective. The discrepancies may be due to different model systems and different signaling pathway involved. Ang II-induced cardiac hypertrophy may be alleviated through regulation of autophagy. This review focuses on Ang II to highlight the molecular targets and pathways identified in the prevention and treatment of Ang II-induced pathological cardiac hypertrophy by regulating autophagy.

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“…Once activated, AMPK leads to the conservation of intracellular ATP levels via multiple downstream pathways, including autophagy (Hardie, 2011). Autophagy is an evolutionary-conserved process for the degradation and recycling of cellular constituents, participating in bioenergetic management during energy stress (Hale et al, 2013). Several lines of evidence suggest that autophagy can be induced by metformin via an AMPK-dependent manner in peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre‐activation of AMPK‐dependent autophagy

Jiang

Zhu

et al. 2014

British J Pharmacology

214

125

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BACKGROUND AND PURPOSERecent clinical trials report that metformin, an activator of AMP-activated protein kinase (AMPK) used to treat type 2 diabetes, significantly reduces the risk of stroke by actions that are independent of its glucose-lowering effects. However, the underlying molecular mechanisms are not known. Here, we tested the possibility that acute metformin preconditioning confers neuroprotection by pre-activation of AMPK-dependent autophagy in a rat model of permanent middle cerebral artery occlusion (pMCAO). EXPERIMENTAL APPROACHMale Sprague-Dawley rats were pretreated with either vehicle, an AMPK inhibitor, Compound C, or an autophagy inhibitor, 3-methyladenine, and were injected with a single dose of metformin (10 mg kg −1 , i.p.). Then, AMPK activity and autophagy biomarkers in the brain were assessed. At 24 h after metformin treatment, rats were subjected to pMCAO; infarct volume, neurological deficits and cell apoptosis were evaluated 24 and 96 h later. KEY RESULTSA single dose of metformin significantly activated AMPK and induced autophagy in the brain. The enhanced autophagic activity was inhibited by Compound C pretreatment. Furthermore, acute metformin preconditioning significantly reduced infarct volume, neurological deficits and cell apoptosis during a subsequent focal cerebral ischaemia. The neuroprotection mediated by metformin preconditioning was fully abolished by Compound C and partially inhibited by 3-methyladenine. CONCLUSIONS AND IMPLICATIONSThese results provide the first evidence that acute metformin preconditioning induces autophagy by activation of brain AMPK, which confers neuroprotection against subsequent cerebral ischaemia. This suggests that metformin, a well-known hypoglycaemic drug, may have a practical clinical use for stroke prevention.

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Autophagy

Cited by 268 publications

References 236 publications

Morphometric analysis of a triple negative breast cancer cell line in hydrogel and monolayer culture environments

Morphometric analysis of a triple negative breast cancer cell line in hydrogel and monolayer culture environments

The role of autophagy in angiotensin II-induced pathological cardiac hypertrophy

Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre‐activation of AMPK‐dependent autophagy

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