Real-time observation of protein aggregates in pharmaceutical formulations using liquid cell electron microscopy

DiMemmo, Lynn M.; Varano, A. Cameron; Haulenbeek, Jonathan; Liang, Yen Nan; Patel, Kaya; Dukes, Madeline J.; Zheng, Songyan; Hubert, Mario; Piccoli, Steven P.; Kelly, Deborah F.

doi:10.1039/c6lc01160h

Cited by 29 publications

(24 citation statements)

References 24 publications

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“…After determining myocardial protein concentrations (Pierce BCA Protein Assay; ThermoFisher) protein aggregate accrual in the heart was measured using a commercially available kit (Proteostat; Enzo Life Sciences)(Laor et al, 2019; Watanabe et al, 2012). Electron microscopy was used as a second approach to estimate cardiac protein aggregates (DiMemmo et al, 2017; Sung et al, 2015). Details concerning each of these methods is provided in online “Experimental procedures.”…”

Section: Methodsmentioning

confidence: 99%

Late-in-life treadmill-training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts

Cho

Ramous

et al. 2021

Preprint

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There is evidence for a progressive decline of protein quality control mechanisms during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age-associated cardiac dysfunction. Macroautophagy (referred to as autophagy) is the process by which post-mitotic cells such as cardiomyocytes clear defective proteins and organelles. We hypothesized that late-in-life exercise training improves autophagy, protein aggregate clearance, and function that is otherwise dysregulated in hearts from old vs adult mice. As expected, 24-month old male C57BL/6J mice (old) exhibited : (i) repressed autophagosome formation and protein aggregate accumulation in the heart; (ii) systolic and diastolic dysfunction; and (iii) reduced exercise capacity, vs. 8-month old (adult) mice (all p< .05). Separate cohorts of 21 month old mice completed a 3-month progressive resistance treadmill-running program (old-ETR) that improved (all < .05) : (i) body composition; (ii) exercise capacity; and (iii) soleus muscle citrate synthase activity, vs. age-matched mice that did not train (old-SED). Importantly, (iv) protein expression of autophagy markers indicated trafficking of the autophagosome to the lysosome increased, (v) protein aggregate clearance improved, and (vi) overall function was enhanced (all p<0.05), in hearts from old-ETR vs. old-SED mice. Dietary maneuvers and pharmacological interventions shown to elevate basal autophagy are reported to mitigate / reverse age-associated cardiac dysfunction. Here we show the first evidence that a physiological intervention initiated late-in-life improves autophagic flux, protein aggregate clearance, and overall function in mouse hearts.

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Section: Methodsmentioning

confidence: 99%

Late-in-life treadmill-training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts

Cho

Ramous

et al. 2021

Preprint

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“…During 2014-2019, liquid cell TEM has been used to investigate micelle-micelle fusion process 48 and self-assembly 49 of amphiphilic block polymers, movements of individual water-soluble polymers 50 and proteins. 16,[51][52]…”

Section: Self-assembly Of Nanomaterialsmentioning

confidence: 99%

Investigating Dynamic Processes of Nanomaterials Using in Situ Liquid Phase TEM Technologies: 2014-2019

Guo¹,

Jiang²,

Peng³

et al. 2020

Eng. Sci.

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The dynamic processes of nanomaterials are common phenomena in material science and biological system. Liquid-phase transmission electron microscopy (TEM) with high resolution provides unprecedented insights into dynamical processes by in situ imaging. This review summarizes the technical developments and the breakthroughs during 2014-2019 in the field of nanoparticles nucleation and growth, nanoparticles corrosion, self-assembly of nanomaterials, dynamical processes in vivo, in situ electrochemistry and radiolysis induced reaction in energy systems. The recent research developments in the liquid-phase TEM will promote advancement for material science and bioscience.

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“…The tendency of spatial resolution is shown on the left side, time and energy resolutions are shown on the right side, respectively. Reproduced with permission . Copyright 2017, Royal Society of Chemistry.…”

Section: Introductionmentioning

confidence: 99%

In Situ Transmission Electron Microscopy Characterization and Manipulation of Two‐Dimensional Layered Materials beyond Graphene

Luo

Wang

et al. 2017

Small

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Real-time observation of protein aggregates in pharmaceutical formulations using liquid cell electron microscopy

Cited by 29 publications

References 24 publications

Late-in-life treadmill-training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts

Late-in-life treadmill-training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts

Investigating Dynamic Processes of Nanomaterials Using in Situ Liquid Phase TEM Technologies: 2014-2019

In Situ Transmission Electron Microscopy Characterization and Manipulation of Two‐Dimensional Layered Materials beyond Graphene

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