BRCC36 Contributes to ACE2 Deubiquitination in Salt-Sensitive Hypertensive Female Mice

Location

LSU Health Sciences Center - New Orleans

Event Website

https://www.medschool.lsuhsc.edu/genetics/2023_medical_student_research_poster_symposium.aspx

Presentation Date

23-10-2023 8:29 AM

Description

According to the Centers for Disease Control and Prevention, hypertension directly contributed to 691,095 deaths in 2021, making it one of the leading causes of death in the United States. The brain renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of hypertension. Angiotensin-II (Ang-II) binds to the Ang-II type 1 receptor (AT1R) and mediates the vasoconstrictive and pro-hypertensive effects. On the other hand, angiotensin-converting enzyme 2 (ACE2) mitigates the pro-hypertensive effects of Ang-II by cleaving it into Ang-(1-7), a vasodilator. We have previously reported that Ang-II mediates the internalization and degradation of ACE2. In hypertensive males, we identified NEDD4-2 and UBR1 as E3 ubiquitin ligases targeting ACE2. Based on discovery proteomics mass spectrometry for hypothalamic tissue extracted from normal and hypertensive mice, BRCC36, a Lys-63-specific deubiquitinase, was observed to be downregulated in hypertensive mice. We further analyzed BRCC36 protein levels in the brain tissues of male and female mice. Baseline BRC336 protein levels were significantly higher in the brain of female mice (6-fold compared to baseline males, p

Comments

Mentors: Drs. Eric Lazartigues1,2,3,4 and Mona Elgazzaz1,2,4 LSUHSC, Cardiovascular Center of Excellence1, Pharmacology Department2, Neuroscience Department3, LSUHSC, Southeast Veterans Healthcare System4

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Oct 23rd, 8:29 AM

BRCC36 Contributes to ACE2 Deubiquitination in Salt-Sensitive Hypertensive Female Mice

LSU Health Sciences Center - New Orleans

According to the Centers for Disease Control and Prevention, hypertension directly contributed to 691,095 deaths in 2021, making it one of the leading causes of death in the United States. The brain renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of hypertension. Angiotensin-II (Ang-II) binds to the Ang-II type 1 receptor (AT1R) and mediates the vasoconstrictive and pro-hypertensive effects. On the other hand, angiotensin-converting enzyme 2 (ACE2) mitigates the pro-hypertensive effects of Ang-II by cleaving it into Ang-(1-7), a vasodilator. We have previously reported that Ang-II mediates the internalization and degradation of ACE2. In hypertensive males, we identified NEDD4-2 and UBR1 as E3 ubiquitin ligases targeting ACE2. Based on discovery proteomics mass spectrometry for hypothalamic tissue extracted from normal and hypertensive mice, BRCC36, a Lys-63-specific deubiquitinase, was observed to be downregulated in hypertensive mice. We further analyzed BRCC36 protein levels in the brain tissues of male and female mice. Baseline BRC336 protein levels were significantly higher in the brain of female mice (6-fold compared to baseline males, p

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