Disease relevance of SLC33A1

• Although homologs of this family of proteins have been identified in lower organisms, such as Escherichia coli, Drosophila melanogaster, and Caenorhabditis. elegans, currently only one member of this SLC33A1 family has been identified in humans [1].
• The AT-1 gene, originally named ACATN (acetyl-CoA transporter), was cloned from human melanoma cells [1].
• CONCLUSIONS: These findings indicate that chronic blockade of Ang II receptors by either site-selective or balanced AT1/AT2 antagonists is insufficient to inhibit intimal hyperplasia after experimental coronary vascular injury in the pig [2].
• OBJECTIVES: Treatment with erythropoietin and AT1 blockers is protective in experimental acute cerebral ischemia, with promising results in pilot clinical studies in human stroke [3].
• Secondary rise of albuminuria under AT1-receptor blockade--what is the potential role of aldosterone escape [4]?

High impact information on SLC33A1

• Immunohistochemical study with an antibody specific to the AT-1 protein suggested that it is most probably expressed in the endoplasmic reticulum membrane [5].
• By expression cloning using COS-1 cells stably transfected with GD3-synthase (COS-1/GD3+) as a recipient cell line, we have isolated a cDNA, termed AT-1, encoding a novel protein required for the formation of O-acetylated (Ac) gangliosides [5].
• METHODS AND RESULTS: In separate studies, three Ang II receptor antagonists, including AT1 selective (L-158,809), balanced AT1/AT2 (L-163,082), and AT2 selective (L-164,282) agents, were evaluated for their ability to inhibit vascular intimal thickening in a porcine coronary artery model of vascular injury [2].
• The change in PKC epsilon distribution and in TnI phosphorylation in diabetic animals was completely prevented by rendering the animals euglycemic with insulin or by concomitant treatment with a specific angiotensin II type-1 receptor (AT1) antagonist [6].
• Promoters for cell death pathway, death receptor 5, cyclins A1 and C, and caspases-1, -3, and -9, were upregulated, whereas cell death inhibitors, acetyl-CoA transporter, and NF-kappaB were also upregulated [7].

Chemical compound and disease context of SLC33A1

• The aim of this study was to investigate the effect of prophylactic treatment with the angiotensin type 1 (AT1) receptor antagonist losartan on right ventricular hypertrophy and cardiac angiotensin 1-converting enzyme (ACE) activity in a rat model of monocrotaline-induced pulmonary hypertension [8].
• We studied the effect of a selective AT1 antagonist, valsartan, on glucose, lipid metabolism and the preheparin LPL mass in 55 patients with type 2 diabetes and hypertension [9].
• Angiotensin II (ANG-II) and its receptor (AT1) have been potential targets of therapy for liver cirrhosis [10].
• Recent studies show that candesartan cilexetil regulates thirst and hypertension in rodents, via cerebral AT1 receptor blockade [11].
• Immunohistochemical studies using the hypoxia marker, pimonidazole, and the vascular endothelial cell marker, CD31, confirmed that the H tumors had more extensive vasculature and less hypoxia than the AT1 tumors [12].

Biological context of SLC33A1

• METHODS: Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium [13].
• Selective AT1 receptor antagonism enhances sympathetically mediated vasoconstriction in man [14].
• Ultrasound induced a 55- (Mewo) to 220-fold (AT1) stimulation resulting in transfection efficiencies in vitro between 2% (Mewo) and 12% (AT1) [15].
• CONCLUSION: The results explain why physiological concentrations of free Ang II far below the equilibrium dissociation constant of its reaction with AT1 receptors are sufficient to increase vascular resistance, and why a correlation between blood pressure and the concentration of free Ang II is often difficult to demonstrate [16].
• This pre-receptor stimulus amplification (PRESTAMP) mechanism is sustained by AT1 receptor-mediated endocytosis and receptor recycling [16].

Anatomical context of SLC33A1

• CONCLUSIONS/INTERPRETATION: AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS [13].
• Using Chinese hamster ovary (CHO) cells expressing cloned Kv7.2 + 7.3 heteromultimers and AT1 receptors studied under perforated patch clamp, angioII induced a strong suppression of the Kv7.2/7.3 current that returned to near baseline within 10 min of stimulation [17].
• Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits neutrophil recruitment in the lung triggered by fMLP [18].
• Using an in vivo radioligand competition assay, in which receptor occupancy is demonstrated via competitive blockade of the in vivo binding of [125I][Sar1,Ile8]angiotensin II to AT1 receptors in rat kidney cortex, we demonstrated that the in vivo pharmacologic potencies reflect receptor occupancy [19].
• The glucuronidation of the AT1 nonpeptide angiotensin II receptor antagonist, SR 47436 (BMS 186295), was investigated in hepatic microsomes prepared from various species, i.e., Sprague-Dawley rat, Cynomolgus monkey and Caucasian humans [20].

Associations of SLC33A1 with chemical compounds

• The acetyl-CoA (Ac-CoA) transporter (AT-1) is a multiple transmembrane protein in the endoplasmic reticulum [1].
• Losartan, an antagonist of Ang II receptor (AT1), abolishes the agonist-dependent stimulation of IRE/protein interaction and the consequent increase in MLC-2v gene transcription [21].
• RESULTS: MAP responses to AT1 receptor inhibition and exogenous Ang II were attenuated in castrated NZGH [22].
• In the first set of experiments, rats eating a low-sodium diet were infused with the AT1 blocker, candesartan, or vehicle [23].
• High-performance liquid chromatographic analysis of anionic phospholipids in CHO cells stably expressing AT1 receptors revealed that PIP2 and phosphatidylinositol 4-phosphate levels are to be strongly depleted after 2 min of stimulation with angioII, with a partial rebound after 10 min [17].

Analytical, diagnostic and therapeutic context of SLC33A1

• METHODS: Mean arterial pressure (MAP) responses to angiotensin II receptor 1 (AT1) inhibition were measured in conscious male New Zealand genetically hypertensive rats (NZGH) subjected to sham operation, castration or castration+testosterone replacement [22].
• We have localized and characterized the expression of Ang II receptor subtypes, AT1 and AT2, in the kidney, interlobular arteries, thoracic aorta, and middle cerebral artery, in children during their first 2 years of life, using quantitative autoradiography [24].
• By indirect immunofluorescence and post-embedding EM gold technique, the localization of alpha 1-adrenergic, M2-muscarinic and angiotensin II receptor-I (AT1) were determinated [25].
• AT1 protein and mRNA levels were assessed by Western blotting and real-time polymerase chain reaction [10].

References