Structural Features Influencing the Bioactive Conformation of Angiotensin II and Angiotensin A: Relationship between Receptor Desensitization, Addiction, and the Blood–Brain Barrier

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 5779 - 5779

Опубликована: Май 26, 2024

The N-terminal portion of the octapeptide angiotensin II (DRVYIHPF; AngII), a vasopressor peptide that favorably binds to, and activates, AngII type 1 receptor (AT1R), has an important role in maintaining bioactive conformation. It involves all three charged groups, namely (i) amino group cation, (ii) Asp sidechain anion (iii) Arg guanidino cation. Neutralization any one these groups results substantial reduction (<5%) bioactivity, implicating specialized function for this cluster. In contrast, A (ARVYIHPF; AngA) reduced bioactivity at AT1R; however, replacement with sarcosine (N-methyl-glycine) not only restores but increases activity agonist, antagonist, inverse agonist analogues. bend produced N-terminus by introduction secondary acid is thought to realign functional chaperone C-terminal AngII, allowing transfer negative charge originating C-terminus be transferred Tyr hydroxyl-forming tyrosinate anion, which required activate desensitizes (tachyphylaxis). Peptide (sarilesin) nonpeptide (sartans) moieties, are long-acting agonists, appear desensitize mechanism analogous tachyphylaxis. Sartans/bisartans were found bind alpha adrenergic receptors resulting structure-dependent desensitization or resensitization. These considerations have provided information on mechanisms desensitization/tolerance insights into possible avenues treating addiction. regard sartans, cross blood–brain barrier more readily than bisartans, preferred drug candidates.

Язык: Английский

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Longevity-Associated Transcription Factor ATF7 Promotes Healthspan by Suppressing Cellular Senescence and Systematic Inflammation

Aging and Disease, Год журнала: 2022, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2022

Aging is characterized by persistent low-grade systematic inflammation, which largely responsible for the occurrence of various age-associated diseases. We and others have previously reported that long-lived people (such as centenarians) can delay onset or even escape certain major age-related Here, screening blood transcriptome inflammatory profiles, we found individuals had a relatively lower inflammation level (IL6, TNFα), accompanied up-regulation activating transcription factor 7 (ATF7). Interestingly, ATF7 expression was gradually reduced during cellular senescence. Loss induced senescence, while overexpression delayed senescence progress senescence-associated secretory phenotype (SASP) secretion. showed anti-senescence effects were achieved inhibiting nuclear kappa B (NF-κB) signaling increasing histone H3K9 dimethylation (H3K9me2). In Caenorhabditis elegans, significantly suppressed aging biomarkers extended lifespan. Our findings suggest longevity-promoting lowers in individuals.

Язык: Английский

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Brain Renin–Angiotensin System: From Physiology to Pathology in Neuronal Complications Induced by SARS-CoV-2

Analytical Cellular Pathology, Год журнала: 2023, Номер 2023, С. 1 - 12

Опубликована: Авг. 4, 2023

Angiotensin-converting enzyme 2 (ACE2), a key in the renin–angiotensin system (RAS), is expressed various tissues and organs, including central nervous (CNS). The spike protein of severe acute respiratory syndrome coronavirus (SARS-CoV-2), virus responsible for disease-2019 (COVID-19), binds to ACE2, which raises concerns about potential viral infection CNS. There are numerous reports suggesting link between SARS-CoV-2 neurological manifestations. This study aimed present an updated review role brain RAS components, especially complications induced by infection. Several routes entry into have been proposed. Because anosmia condition appeared broadly COVID-19 patients, olfactory nerve route was suggested as early pathway brain. In addition, hematogenous via disintegrations blood–brain barrier following increase systemic cytokine chemokine levels retrograde axonal transport, vagus innervating lungs, described. Common nonspecific symptoms patients myalgia, headache, anosmia, dysgeusia. However, more outcomes include cerebrovascular diseases, cognitive impairment, anxiety, encephalopathy, stroke. Alterations components such angiotensin II (Ang II) ACE2 mediate manifestations infection, at least part. Downregulation due followed Ang levels, leads hyperinflammation oxidative stress, turn accelerates neurodegeneration Furthermore, downregulation hypothalamus induces stress anxiety responses increasing corticotropin-releasing hormone. may also dysregulate CNS neurotransmission, leading observed cases COVID-19. It can be concluded that partially associated with changes components.

Язык: Английский

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SARS-CoV-2 may play a direct role in the pathogenesis of posterior reversible encephalopathy syndrome (PRES) associated with COVID-19: A CARE-compliant case report and literature review

Medicine, Год журнала: 2024, Номер 103(5), С. e37192 - e37192

Опубликована: Фев. 2, 2024

Rationale: During the past 3 years of corona virus disease 2019 (COVID-19) pandemic, COVID-19 has been recognized to cause various neurological complications, including rare posterior reversible encephalopathy syndrome (PRES). In previously reported cases PRES associated with COVID-19, majority patients had severe infection and known predisposing factors for PRES, such as uncontrolled hypertension, renal dysfunction, use immunosuppressants. It remains unclear whether these risk or acute respiratory coronavirus 2 (SARS-CoV-2) contributes development in patients. Here we report a special case without any indicating SARS-CoV-2’s direct role pathogenesis COVID-19. Patient concerns: An 18-year-old female patient presented emergency department abdominal pain. Preliminary investigations showed no abnormalities, except positive results novel nucleic acid tests using oropharyngeal swabs. However, subsequently developed tonic–clonic seizures, headaches, vomiting on second day. Extensive have performed, brain MRI lumbar puncture. Brain hypointense T1-weighted hyperintense T2-weighted lesions bilateral occipital, frontal, parietal cortices enhancement effect. Blood cerebrospinal fluid analyses yielded negative results. The insufficiency, autoimmune disease, immunosuppressants cytotoxic drugs. Diagnoses: was diagnosed based clinical features typical findings PRES. Interventions: Symptomatic treatments anticonvulsants were administered Outcomes: fully recovered within 1 week. initial abnormalities also disappeared completely MR examination performed 11 days later, supporting diagnosis followed up 6 months remained normal state. Lessons: current classical that although may be multifactorial, SARS-CoV-2 play

Язык: Английский

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Exploring the Th2 Response in Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Potential Modulator of the Renin-Angiotensin System (RAS) Pathway in Hypertension Development

Life, Год журнала: 2024, Номер 14(9), С. 1080 - 1080

Опубликована: Авг. 29, 2024

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic (MASLD), is alarmingly increasing alongside the cases of obesity worldwide. MASLD an underestimated abnormality closely linked with a higher risk developing systemic arterial hypertension (SAH). However, underlying mechanism association between and SAH remains unknown. Inflammation may link these two entities by regulating renin-angiotensin system (RAS). For this reason, in study, we evaluated hepatic expression cytokine profile critical molecules RAS pathway patients morbid MASLD, both SAH. We found statistically significant correlation ACE levels cytokines IL-4, IL-10, IL-13 Th2 response. Furthermore, according multiple linear regression analysis, IL-4 were best predictors levels. Moreover, observed increased obesity, compared those without These results allow us propose, for first time, that response, through RAS, could play role individuals obesity.

Язык: Английский

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Neurological Diseases Define the Cytokine Profile in CFS during SARS-CoV-2 Infection in Highly Ill Patients

Tropical Medicine and Infectious Disease, Год журнала: 2023, Номер 8(6), С. 290 - 290

Опубликована: Май 25, 2023

Neuroinflammation is critical in developing and progressing neurological diseases. The underlying pro-inflammatory cytokine expression combined with additional mechanisms the neuropathology, such as oxidative stress, brain-blood barrier damage, endothelial dysfunction, could contribute to susceptibility severe COVID-19. physiopathology of SARS-CoV-2 other human coronaviruses (H-CoVs) has not been completely understood; however, they have all linked a disproportionated response immune system, particularly an exacerbated production dysregulation total cell counts. In this article, based on compilation studies reported by our working group regarding COVID-19 diseases, we propose that inflammation observed central nervous through CSF analysis, be conditioned disease(s) enhanced Therefore, it necessary determine profile different disorders adequate treatments avoid forms disease these patients.

Язык: Английский

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COVID-19: Potassium Contributes to Pathologies that Cause Disability

Infectious Disorders - Drug Targets, Год журнала: 2023, Номер 23(7)

Опубликована: Июнь 23, 2023

Язык: Английский

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INTERSEÇÃO VIRAL: ANÁLISE DOS EFEITOS NEUROLÓGICOS PÓS-COVID NO SISTEMA NERVOSO

Опубликована: Март 5, 2024

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OS EFEITOS DA CL EM OUTROS SISTEMAS CORPORAIS

Опубликована: Март 5, 2024

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INTRODUÇÃO

Опубликована: Март 5, 2024

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