The Actin Bundling Protein Fascin-1 as an ACE2-Accessory Protein

Ogunlade, Blessing; Guidry, Jessie; Mukerjee, Snigdha; Sriramula, Srinivas; Lazartigues, Eric; Filipeanu, Catalin M.

doi:10.1007/s10571-020-00951-x

Cited by 9 publications

(9 citation statements)

References 44 publications

(77 reference statements)

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“…The actin bundle protein fascin‐1 regulates the expression level and subcellular localization of ACE2. 27 Thus, we detected the morphology of F‐actin by phalloidin labeling green fluorescence staining and found obvious actin polymerization and stable actin bundles in HEK293T‐ACE2 cells (Figure 5A ) and HUVECs (Figure 5B ) at pH 7.4, that is, normal blood pH conditions. Additionally, polymerization of F‐actin was stable in pH 7.8 medium.…”

Section: Resultsmentioning

confidence: 90%

“…The actin bundling protein fascin‐1 regulates the expression levels and subcellular localization of ACE2. 27 With regard to infection by another kind of human coronavirus, NL63, which also needs to interact with ACE2, actin cortex remodeling is required for virus endocytosis. 28 Changes in pH can influence actin polymerization and depolymerization.…”

Section: Introductionmentioning

confidence: 99%

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Nanoantidote for repression of acidosis pH promoting COVID‐19 infection

Liu

Ruan

Sheng

et al. 2022

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Acidosis, such as respiratory acidosis and metabolic acidosis, can be induced by coronavirus disease 2019 (COVID‐19) infection and is associated with increased mortality in critically ill COVID‐19 patients. It remains unclear whether acidosis further promotes SARS‐CoV‐2 infection in patients, making virus removal difficult. For antacid therapy, sodium bicarbonate poses great risks caused by sodium overload, bicarbonate side effects, and hypocalcemia. Therefore, new antacid antidote is urgently needed. Our study showed that an acidosis‐related pH of 6.8 increases SARS‐CoV‐2 receptor angiotensin‐converting enzyme 2 (ACE2) expression on the cell membrane by regulating intracellular microfilament polymerization, promoting SARS‐CoV‐2 pseudovirus infection. Based on this, we synthesized polyglutamic acid‐PEG materials, used complexation of calcium ions and carboxyl groups to form the core, and adopted biomineralization methods to form a calcium carbonate nanoparticles (CaCO3‐NPs) nanoantidote to neutralize excess hydrogen ions (H+), and restored the pH from 6.8 to approximately 7.4 (normal blood pH). CaCO3‐NPs effectively prevented the heightened SARS‐CoV‐2 infection efficiency due to pH 6.8. Our study reveals that acidosis‐related pH promotes SARS‐CoV‐2 infection, which suggests the existence of a positive feedback loop in which SARS‐CoV‐2 infection‐induced acidosis enhances SARS‐CoV‐2 infection. Therefore, antacid therapy for acidosis COVID‐19 patients is necessary. CaCO3‐NPs may become an effective antacid nanoantidote superior to sodium bicarbonate.

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Section: Resultsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Nanoantidote for repression of acidosis pH promoting COVID‐19 infection

Liu

Ruan

Sheng

et al. 2022

VIEW

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“…Western blots were performed on primary hypothalamic neuronal homogenates, as described previously [20,40]. Neuron samples were homogenized in 1X lysis buffer containing protease and phosphatase inhibitors cocktail (Roche) and incubated on ice for 15 min.…”

Section: Protein Analysis By Western Blotmentioning

confidence: 99%

Activation of Kinin B1R Upregulates ADAM17 and Results in ACE2 Shedding in Neurons

Parekh

Sriramula

2020

IJMS

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Angiotensin converting enzyme 2 (ACE2) is a critical component of the compensatory axis of the renin angiotensin system. Alterations in ACE2 gene and protein expression, and activity mediated by A Disintegrin And Metalloprotease 17 (ADAM17), a member of the “A Disintegrin And Metalloprotease” (ADAM) family are implicated in several cardiovascular and neurodegenerative diseases. We previously reported that activation of kinin B1 receptor (B1R) in the brain increases neuroinflammation, oxidative stress and sympathoexcitation, leading to the development of neurogenic hypertension. We also showed evidence for ADAM17-mediated ACE2 shedding in neurons. However, whether kinin B1 receptor (B1R) activation has any role in altering ADAM17 activity and its effect on ACE2 shedding in neurons is not known. In this study, we tested the hypothesis that activation of B1R upregulates ADAM17 and results in ACE2 shedding in neurons. To test this hypothesis, we stimulated wild-type and B1R gene-deleted mouse neonatal primary hypothalamic neuronal cultures with a B1R-specific agonist and measured the activities of ADAM17 and ACE2 in neurons. B1R stimulation significantly increased ADAM17 activity and decreased ACE2 activity in wild-type neurons, while pretreatment with a B1R-specific antagonist, R715, reversed these changes. Stimulation with specific B1R agonist Lys-Des-Arg9-Bradykinin (LDABK) did not show any effect on ADAM17 or ACE2 activities in neurons with B1R gene deletion. These data suggest that B1R activation results in ADAM17-mediated ACE2 shedding in primary hypothalamic neurons. In addition, stimulation with high concentration of glutamate significantly increased B1R gene and protein expression, along with increased ADAM17 and decreased ACE2 activities in wild-type neurons. Pretreatment with B1R-specific antagonist R715 reversed these glutamate-induced effects suggesting that indeed B1R is involved in glutamate-mediated upregulation of ADAM17 activity and ACE2 shedding.

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“…Fascin represents a family of active binding proteins that are localized in stress fibers and throughout the proliferation of various cells, such as myoblasts and glioma cells ( Ogunlade et al ., 2020 ). This protein is unique to muscle and cell types, such as glial cells, neurons, antigen-presenting dendritic cells, and endothelial cells ( Zhang et al ., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular genotyping, histopathological and immunohistochemical studies of bovine papillomatosis

Gharban¹,

Shaeli²,

Hussen³

2023

Open Vet J

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Background: Bovine papillomatosis (BP) is considered the most common health problem in large cattle farms. Aim: This study attempts to confirm clinically suspected BP in cattle by PCR assay, histopathology, IHC, and genotyping analysis of local isolates. Methods: According to morphological appearance and lesion features, a cross sectional study of 54 clinically diagnosed BP cattle was assigned to this current investigation from May to August (2021) in Al-Kut district (Wasit Province, Iraq) private veterinary clinics using purposive sampling technique based on set criteria. The cattle were diagnosed clinically, and the tissues were collected and some fixed in 10% neutral buffered formalin and other stored frozen and examined by histopathological technique, immunohistochemistry, and PCR assays. Results: Using PCR assay, all cattle were positive for the BPV L1 gene. According to detect the L1 gene, analysis of the phylogenetic tree showed that local BPV cattle isolates were closely related to the NCBI-BLAST BPV type-1 and type-2 of the Polish equine isolate (KF284133.1) and BPV Brazilian Bos taurus isolate (MH187961.1), respectively. Histological detection showed there were acanthosis, hperkeratosis, epidermal thickening, severe infiltration of mononuclear cells, massive hemorrhage, dermal fibroplasia, multifocal spongiosis, moderate neovascularization, moderate to severe elongation of the retention ridge towards the dermis, parakeratosis, rings of calcification, and necrosis with nuclear pyknosis of some spinosum cells. Immunohistochemical findings of tumor necrosis factor-alpha (TNF-), epidermal growth factor receptor (EGFR) and Fascin showed a significant variation in values of immunoreaction in the dermis and epidermis. These results ranged from negative (0) to mild positive (+1) to moderate positive (+2) reactions. Conclusion: The study provided essential molecular and genotyping data to improve our knowledge by emphasizing the crucial of IHC as an elegant diagnostic method to detect cellular alterations.

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The Actin Bundling Protein Fascin-1 as an ACE2-Accessory Protein

Cited by 9 publications

References 44 publications

Nanoantidote for repression of acidosis pH promoting COVID‐19 infection

Nanoantidote for repression of acidosis pH promoting COVID‐19 infection

Activation of Kinin B1R Upregulates ADAM17 and Results in ACE2 Shedding in Neurons

Molecular genotyping, histopathological and immunohistochemical studies of bovine papillomatosis

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