Medicine and Health Sciences Commons^™

The Possible Role Of A Bacterial Aspartate Β-Decarboxylase In The Biosynthesis Of Alamandine, Shalinee Jha, Robert C. Speth, Peter Macheroux

HPD Articles

The understanding of the renin-angiotensin system (RAS) has significantly expanded over the last two decades. The elucidation of angiotensin-converting enzyme 2 (ACE2) that converts angiotensin (Ang) II into Ang (1-7) led to the discovery of the cardio-protective axis of the RAS. In addition, novel components of the system, Angiotensin A (Ang A) and alamandine have been identified. Like Ang (1-7), alamandine is a vasodilator and can counteract the effects of Ang II by increasing nitric oxide release from the endothelium and decreasing nicotinamide adenine dinucleotide phosphate oxidase (NADPH)-related superoxide production. Theoretically, alamandine can be derived from Ang (1-7) by decarboxylation …

The Apoptotic Effect Of Gsk-3 Inhibitors: Bio And Chir 98014 On H1975 Lung Cancer Cells Through Ros Generation And Mitochondrial Dysfunction., Theodore Lemuel Mathuram, Thiagarajan Venkatesan, Jayanta Das, Umamaheswari Natarajan, Appu Rathinavelu

HPD Articles

OBJECTIVE: GSK-3 has been reported to be upregulated in malignant diseases, including lung cancers, thus suggesting it to be a valid target for cancer treatment. The study elucidates the possible mechanism involved in the ability of GSK-3 inhibitors: BIO and CHIR 98014 to regulate proteins involved in cell death of H1975 lung cancer cells.

RESULTS: BIO and CHIR 98014 successfully induced apoptosis at lower concentrations in H1975 cells but not in H460 lung cancer cells. Moreover, increased ROS generation and depolarization of mitochondrial membrane potential were observed in both treatments. Cleavage of caspase-3 was observed in both BIO and CHIR …

Sex-Specific Modulation Of Blood Pressure And The Renin-Angiotensin System By Ace (Angiotensin-Converting Enzyme) 2, Hong Ji, Aline M. De Souza, Bilkish Bajaj, Wei Zheng, Xie Wu, Robert C. Speth, Kathryn Sandberg

HPD Articles

We showed ACE (angiotensin-converting enzyme) 2 is higher in the kidney of male compared with female mice. To further investigate this sex difference, we examined the role of ACE2 in Ang-[1-8] (angiotensin [1-8])-induced hypertension and regulation of the renin-angiotensin system in the kidney of WT (wild type) and Ace2 KO (knockout) mice. Mean arterial pressure rose faster in WT male than WT female mice after Ang-[1-8] infusion. This sex difference was attenuated in ACE2 KO mice. Ang-[1-8] infusion reduced glomerular AT1R (angiotensin type 1 receptor) binding in WT female mice by 30%, and deletion of abolished this effect. In contrast, …

Angiotensin Ii Administration To Covid-19 Patients Is Not Advisable, Robert C. Speth

HPD Articles

No abstract provided.

Keep Taking Your Ace Inhibitors And Arbs During The Covid 19 Pandemic, Robert C. Speth

HPD Articles

No abstract provided.

Incorporation Of Agouti-Related Protein (Agrp) Human Single Nucleotide Polymorphisms (Snps) In The Agrp-Derived Macrocyclic Scaffold C[Pro-Arg-Phe-Phe-Asn-Ala-Phe-Dpro] Decreases Melanocortin-4 Receptor Antagonist Potency And Results In The Discovery Of Melanocortin-5 Receptor Antagonists, Zoe M. Koerperich, Mark D. Ericson, Katie T. Freeman, Robert C. Speth, Irina D. Pogozheva, Henry I. Mosberg, Carrie Haskell-Luevano

HPD Articles

While the melanocortin receptors (MCRs) are known to be involved in numerous biological pathways, the potential roles of the MC5R have not been clearly elucidated in humans. Agouti-related protein (AgRP), an MC3R/MC4R antagonist and MC4R inverse agonist, contains an exposed β-hairpin loop composed of six residues (Arg-Phe-Phe-Asn-Ala-Phe) that is imperative for binding and function. Within this active loop of AgRP, four human missense polymorphisms were deposited into the NIH Variation Viewer database. These polymorphisms, Arg111Cys, Arg111His, Phe112Tyr, and Ala115Val (AgRP full-length numbering), were incorporated into the peptide macrocycles c[Pro-Arg-Phe-Phe-Xaa-Ala-Phe-dPro], where Xaa was Dap or Asn, to explore the functional effects …

Severe Food Restriction Activates The Central Renin Angiotensin System, Aline Maria De Souza, Andrea Linares, Robert C. Speth, Glenda V. Campos, Hong Ji, Deoclécio Chianca, Kathryn Sandberg, Rodrigo C. De Menezes

HPD Articles

We previously showed that 2 weeks of a severe food restricted (sFR) diet (40% of the caloric intake of the control (CT) diet) up-regulated the circulating renin angiotensin (Ang) system (RAS) in female Fischer rats, most likely as a result of the fall in plasma volume. In this study, we investigated the role of the central RAS in the mean arterial pressure (MAP) and heart rate (HR) dysregulation associated with sFR. Although sFR reduced basal mean MAP and HR, the magnitude of the pressor response to intracerebroventricular (icv) microinjection of Ang-[1-8] was not affected; however, HR was 57 ± 13 …