Effect of hyperglycemia and rosiglitazone on renal and urinary neprilysin in<i>db</i>/<i>db</i>diabetic mice

Alawi, Laale F.; Emberesh, Sana E; Owuor, Brenda A.; Chodavarapu, Harshita; Fadnavis, Rucha; El‐Amouri, Salim S.; Elased, Khalid M.

doi:10.14814/phy2.14364

Cited by 12 publications

(13 citation statements)

References 62 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, rosiglitazone increased vascular ACE2 expression in hypertensive, but not in normotensive rats ( Sanchez-Aguilar et al, 2019 ). In transgenic diabetic mice, rosiglitazone downregulated renal ADAM17 expression, decreased ACE2 shedding and reduced urinary soluble ACE2, thereby increasing ACE2 protection of the kidneys without altering renal ACE2 expression ( Alawi et al, 2020 ; Chodavarapu et al, 2013 ). Notably, although rosiglitazone induced an upregulation of ACE2 mRNA and protein expression in adipocytes of wild type mice, this ACE2 increase was markedly attenuated in adipocytes of fibroblast growth factor 21 (FGF21) knockout mice ( Pan et al, 2018 ), suggesting that endogenous FGF21 in adipocytes modulates ACE2 expression in an autocrine manner.…”

Section: Antidiabetic Drugs and Ace2mentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

View full text Add to dashboard Cite

The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.

show abstract

Section: Antidiabetic Drugs and Ace2mentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

View full text Add to dashboard Cite

show abstract

“…Final absorbance was read at 450 nm using Fusion Packard plate reader (Packard BioScience, Meriden, CT, United States). Urinary creatinine levels were measured using an assay kit purchased from Quidel Corporation (San Diego, CA, United States) as described before ( Alawi et al, 2020 ). Briefly, urine samples and standards were diluted to 1:40 and 25 µl of this diluted samples and standards were added to 96 well plate followed by 75 µl of colored solution and incubated at RT for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…Renal and urinary NEP activity were measured using an indirect fluorogenic assay as described before ( Alawi et al, 2020 ) with some modifications. The cleavage of the fluorogenic substrate, Succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin (Suc-Ala-Ala-Phe-AMC) (Sigma-Aldrich, St. Louis, MO, United States) by NEP generates hydrophobic residue (phenyalanine-methylcouramin).…”

Section: Methodsmentioning

confidence: 99%

Effects of Angiotensin II Type 1A Receptor on ACE2, Neprilysin and KIM-1 in Two Kidney One Clip (2K1C) Model of Renovascular Hypertension

et al. 2021

Self Cite

View full text Add to dashboard Cite

Activation of the renin angiotensin system plays a pivotal role in the regulation of blood pressure, which is mainly attributed to the formation of angiotensin-II (Ang II). The actions of Ang II are mediated through binding to the Ang-II type 1 receptor (AT1R) which leads to increased blood pressure, fluid retention, and aldosterone secretion. In addition, Ang II is also involved in cell injury, vascular remodeling, and inflammation. The actions of Ang II could be antagonized by its conversion to the vasodilator peptide Ang (1–7), partly generated by the action of angiotensin converting enzyme 2 (ACE2) and/or neprilysin (NEP). Previous studies demonstrated increased urinary ACE2 shedding in the db/db mouse model of diabetic kidney disease. The aim of the study was to investigate whether renal and urinary ACE2 and NEP are altered in the 2K1C Goldblatt hypertensive mice. Since AT1R is highly expressed in the kidney, we also researched the effect of global deletion of AT1R on renal and urinary ACE2, NEP, and kidney injury marker (KIM-1). Hypertension and albuminuria were induced in AT1R knock out (AT1RKO) and WT mice by unilateral constriction of the renal artery of one kidney. The 24 h mean arterial blood pressure (MAP) was measured using radio-telemetry. Two weeks after 2K1C surgery, MAP and albuminuria were significantly increased in WT mice compared to AT1RKO mice. Results demonstrated a correlation between MAP and albuminuria. Unlike db/db diabetic mice, ACE2 and NEP expression and activities were significantly decreased in the clipped kidney of WT and AT1RKO compared with the contralateral kidney and sham control (p < 0.05). There was no detectable urinary ACE2 and NEP expression and activity in 2K1C mice. KIM-1 was significantly increased in the clipped kidney of WT and AT1KO (p < 0.05). Deletion of AT1R has no effect on the increased urinary KIM-1 excretion detected in 2K1C mice. In conclusion, renal injury in 2K1C Goldblatt mouse model is associated with loss of renal ACE2 and NEP expression and activity. Urinary KIM-1 could serve as an early indicator of acute kidney injury. Deletion of AT1R attenuates albuminuria and hypertension without affecting renal ACE2, NEP, and KIM-1 expression.

show abstract

“…High levels of ACE2 protein expression have been detected in mammalian, including human, kidney (Gembardt et al, 2005;Koka et al, 2008;Reich et al, 2008;Giani et al, 2012;Mitani et al, 2014;Grobe et al, 2015;Shi et al, 2015;Larouche-Lebel et al, 2019;Alawi et al, 2020). Strong signals were reported in the brush border of the proximal tubular cells, whereas weak to moderate signals could be found in the glomeruli, Henle's loop, distal tubules, and collecting duct (Hamming et al, 2004;Lely et al, 2004;Kamilic et al, 2010;Giani et al, 2012;Bae et al, 2015;Cao et al, 2017;Errarte et al, 2017).…”

Section: Tissue Distribution Of Ace2mentioning

confidence: 99%

ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives

Saponaro

Rutigliano

Sestito

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

Angiotensin-converting enzyme 2 (ACE2) is related to ACE but turned out to counteract several pathophysiological actions of ACE. ACE2 exerts antihypertensive and cardioprotective effects and reduces lung inflammation. ACE2 is subjected to extensive transcriptional and post-transcriptional modulation by epigenetic mechanisms and microRNAs. Also, ACE2 expression is regulated post-translationally by glycosylation, phosphorylation, and shedding from the plasma membrane. ACE2 protein is ubiquitous across mammalian tissues, prominently in the cardiovascular system, kidney, and intestine. ACE2 expression in the respiratory tract is of particular interest, in light of the discovery that ACE2 serves as the initial cellular target of severe acute respiratory syndrome (SARS)-coronaviruses, including the recent SARS-CoV2, responsible of the COronaVIrus Disease 2019 (COVID-19). Since the onset of the COVID-19 pandemic, an intense effort has been made to elucidate the biochemical determinants of SARS-CoV2-ACE2 interaction. It has been determined that SARS-CoV2 engages with ACE2 through its spike (S) protein, which consists of two subunits: S1, that mediates binding to the host receptor; S2, that induces fusion of the viral envelope with the host cell membrane and delivery of the viral genome. Owing to the role of ACE2 in SARS-CoV2 pathogenicity, it has been speculated that medical conditions, i.e., hypertension, and/or drugs, i.e., ACE inhibitors and angiotensin receptor blockers, known to influence ACE2 density could alter the fate of SARS-CoV-2 infection. The debate is still open and will only be solved when results of properly designed experimental and clinical investigations will be made public. An interesting observation is, however that, upon infection, ACE2 activity is reduced either by downregulation or by shedding. These events might precipitate the so-called "cytokine storm" that characterizes the most severe COVID-19 forms. As evidence accumulates, ACE2 appears a druggable target in the attempt to limit virus entry and replication. Strategies aimed at blocking ACE2 with antibodies, small molecules or peptides, or at neutralizing the virus by competitive binding with exogenously administered ACE2, are currently under investigations. In this review, we will present an overview of the state-of-the-art knowledge on ACE2 biochemistry and pathophysiology, outlining open issues in the context of COVID-19 disease and potential experimental and clinical developments.

show abstract

Effect of hyperglycemia and rosiglitazone on renal and urinary neprilysin indb/dbdiabetic mice

Cited by 12 publications

References 62 publications

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Effects of Angiotensin II Type 1A Receptor on ACE2, Neprilysin and KIM-1 in Two Kidney One Clip (2K1C) Model of Renovascular Hypertension

ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives

Contact Info

Product

Resources

About