Benzyl Alcohol‐Induced Destabilization of Interferon‐γ: A Study by Hydrogen‐Deuterium Isotope Exchange

Tobler, Scott A.; Holmes, Bryan W.; Cromwell, Mary; Fernandez, Erik J.

doi:10.1002/jps.10589

Cited by 41 publications

(30 citation statements)

References 24 publications

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“…In a Bacillus subtilis strain, the lethal concentration of BzA increased the membrane fluidity (43). For protein structures, BzA induced the aggregation of proteins, such as human interleukin (44) and interleukin-1 receptor antagonist (45), by partially unfolding these proteins (46,47). Unfolding actions were also reported for short-chain alcohols (48).…”

Section: Discussionmentioning

confidence: 93%

Pentanol and Benzyl Alcohol Attack Bacterial Surface Structures Differently

Yano

Miyahara

Morii

et al. 2016

Appl Environ Microbiol

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bThe genus Methylobacterium tolerates hygiene agents like benzalkonium chloride (BAC), and infection with this organism is an important public health issue. Here, we found that the combination of BAC with particular alcohols at nonlethal concentrations in terms of their solitary uses significantly reduced bacterial viability after only 5 min of exposure. Among the alcohols, Raman spectroscopic analyses showed that pentanol (pentyl alcohol [PeA]) and benzyl alcohol (BzA) accelerated the cellular accumulation of BAC. Fluorescence spectroscopic assays and morphological assays with giant vesicles indicated that PeA rarely attacked membrane structures, while BzA increased the membrane fluidity and destabilized the structures. Other fluorescent spectroscopic assays indicated that PeA and BzA inactivate bacterial membrane proteins, including an efflux pump for BAC transportation. These findings suggested that the inactivation of membrane proteins by PeA and BzA led to the cellular accumulation but that only BzA also enhanced BAC penetration by membrane fluidization at nonlethal concentrations.

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Section: Discussionmentioning

confidence: 93%

Pentanol and Benzyl Alcohol Attack Bacterial Surface Structures Differently

Yano

Miyahara

Morii

et al. 2016

Appl Environ Microbiol

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“…There are two pathways that a molecule can take from the ocular surface to the posterior part of the eye: 1) through the cornea, vitreous, and retina to the RPE apical surface or 2) through the conjunctiva, sclera, and choriocapillaris to the basolateral surface of the RPE. The latter route is more likely, given the size (15-25 kDa) and hydrodynamic radius (2.6 nm) of IFN␥ (68) and the fact that the RPE is essentially impermeable to Ն20-kDa molecules (37). Since the sclera is highly permeable to molecules with molecular radius as large as 8 nm (2) and with the assumption that, as in human RPE, IFN␥ receptors are mainly located at the basolateral membrane of rat RPE, these in vivo results strongly favor the scleral route to the RPE basolateral membrane.…”

Section: Discussionmentioning

confidence: 97%

IFNγ regulates retinal pigment epithelial fluid transport

Maminishkis

Banzon

et al. 2009

American Journal of Physiology-Cell Physiology

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The present experiments show that IFNgamma receptors are mainly localized to the basolateral membrane of human retinal pigment epithelium (RPE). Activation of these receptors in primary cultures of human fetal RPE inhibited cell proliferation and migration, decreased RPE mitochondrial membrane potential, altered transepithelial potential and resistance, and significantly increased transepithelial fluid absorption. These effects are mediated through JAK-STAT and p38 MAPK signaling pathways. Second messenger signaling through cAMP-PKA pathway- and interferon regulatory factor-1-dependent production of nitric oxide/cGMP stimulated the CFTR at the basolateral membrane and increased transepithelial fluid absorption. In vivo experiments using a rat model of retinal reattachment showed that IFNgamma applied to the anterior surface of the eye can remove extra fluid deposited in the extracellular or subretinal space between the retinal photoreceptors and RPE. Removal of this extra fluid was blocked by a combination of PKA and JAK-STAT pathway inhibitors injected into the subretinal space. These results demonstrate a protective role for IFNgamma in regulating retinal hydration across the outer blood-retinal barrier in inflammatory disease processes and provide the basis for possible therapeutic interventions.

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“…In the EX1 limit, the mass spectrum of a labeled protein will appear as a bimodal distribution, with the low mass peak representing protein molecules that have not unfolded during the labeling period, while the heavy mass peak consists of molecules that have unfolded (Deng et al, 1999;Ferraro and Robertson, 2004;Tobler et al, 2004). The amplitude of the low mass peak decreases with time as that of the heavy mass peak increases.…”

Section: Theoretical Aspects the Four-state Model Of Protein Adsorptimentioning

confidence: 97%

Protein instability during HIC: Evidence of unfolding reversibility, and apparent adsorption strength of disulfide bond‐reduced α‐lactalbumin variants

Deitcher

Xiao

O’Connell

et al. 2009

Biotech & Bioengineering

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A two-conformation, four-state model has been proposed to describe protein adsorption and unfolding behavior on hydrophobic interaction chromatography (HIC) resins. In this work, we build upon previous study and application of a four-state model to the effect of salt concentration on the adsorption and unfolding of the model protein alpha-lactalbumin in HIC. Contributions to the apparent adsorption strength of the wild-type protein from native and unfolded conformations, obtained using a deuterium labeling technique, reveal the free energy change and kinetics of unfolding on the resin, and demonstrate that surface unfolding is reversible. Additionally, variants of alpha-lactalbumin in which one of the disulfide bonds is reduced were synthesized to examine the effects of conformational stability on apparent retention. Below the melting temperatures of the wild-type protein and variants, reduction of a single disulfide bond significantly increases the apparent adsorption strength (approximately 6-8 kJ/mol) due to increased instability of the protein. Finally, the four-state model is used to accurately predict the apparent adsorption strength of a disulfide bond-reduced variant.

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Benzyl Alcohol‐Induced Destabilization of Interferon‐γ: A Study by Hydrogen‐Deuterium Isotope Exchange

Cited by 41 publications

References 24 publications

Pentanol and Benzyl Alcohol Attack Bacterial Surface Structures Differently

Pentanol and Benzyl Alcohol Attack Bacterial Surface Structures Differently

IFNγ regulates retinal pigment epithelial fluid transport

Protein instability during HIC: Evidence of unfolding reversibility, and apparent adsorption strength of disulfide bond‐reduced α‐lactalbumin variants

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