Disease relevance of Agtrl1

• Using stably transfected cells expressing a pertussis toxin-insensitive alpha(i) subunit, we demonstrated that each apelin fragment promoted coupling of the apelin receptor to either Galpha(i1) or Galpha(i2) but not to Galpha(i3) [1].
• In addition, we carried out histology and immunohistochemistry to assess cardiac hypertrophy and to localize apelin and APJ in the adult and embryonic mouse heart [2].
• In addition, MSR knockout mice are more susceptible to L. monocytogenes and HSV-1 infection, indicating a role for MSR in host defense against various pathogens [3].

High impact information on Agtrl1

• To address the physiological significance of the existence of dual ligands for a single receptor, we first compared the ability of the apelin fragments to regulate intracellular effectors, to promote G protein coupling, and to desensitize the response in Chinese hamster ovary cells expressing the murine apelin receptor [1].
• Incubation of macrophages with a cholesterol acceptor particle resulted in a dose-dependent decrease in MSR mRNA expression, which paralleled cholesterol loss from the cells [4].
• We studied the effect of lipoproteins, native and modified LDL (acetylated LDL (AcLDL) and OxLDL) on the expression of the MSR in RAW cells, a murine macrophage cell line [4].
• OxLDL did not affect MSR mRNA stability, implying that MSR mRNA was transcriptionally regulated by lipoproteins [4].
• During embryonic development of mouse and frog, APJ receptor is expressed at high levels in endothelial precursor cells and in nascent vascular structures [5].

Biological context of Agtrl1

• Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ [6].
• Apelin strongly accelerated the cell motility in APJ/293T cells, and this activity was abolished by PTx and LY29004 [7].
• In addition, apelin enhanced focal adhesion kinase (FAK) phosphorylation and increased focal adhesion formation with staining for F-actin in APJ/293T cells [7].
• This study examined whether MSR mediates or modulates oxLDL-induced apoptosis [8].
• However, cell death and DNA fragmentation were markedly diminished in the phorbol ester-differentiated MSR-expressing THP-1 cells and Chinese hamster ovary cells, with stable expression of MSR-AI after cDNA transfection when exposed to the same concentrations of oxLDL and 7-KC [8].

Anatomical context of Agtrl1

• There has been much focus recently on the possible functions of apelin, an endogenous ligand for the orphan G-protein-coupled receptor APJ, in cardiovascular and central nervous systems [9].
• The retinal endothelial cell line RF/6A highly expressed both apelin and APJ transcripts, while human umbilical venous endothelial cells (HUVECs) only expressed apelin mRNA [9].
• We found that both apelin and APJ mRNAs were expressed in isolated mouse adipocytes and that apelin mRNA levels increased during the differentiation of 3T3-L1 cells to adipocytes [10].
• G protein-coupled APJ receptor signaling induces focal adhesion formation and cell motility [7].
• Antibody staining, as well as quantitative real time polymerase chain reaction identified expression of both APJ and apelin in embryonic myocardium as early as embryonic day 13 [2].

Associations of Agtrl1 with chemical compounds

• The sequence shares 90% identity with the human APJ receptor and 31% with the rat AT(1A) angiotensin receptor [11].
• As shown for the human APJ receptor, the rat apelin receptor expressed in the cell line was negatively coupled to adenylate cyclase [11].
• Kainic acid (KA) treatment induced MSR and MAMA mRNA levels on different schedules in brain regions that are susceptible to KA, including hippocampal areas CA1 and CA3 [12].

Physical interactions of Agtrl1

• The apelin receptor is coupled to Gi1 or Gi2 protein and is differentially desensitized by apelin fragments [1].

Analytical, diagnostic and therapeutic context of Agtrl1

• Immunohistochemistry studies revealed APJ staining of myocardial cells in all regions of the adult mouse heart [2].
• In situ hybridization analysis of apelin receptor mRNA expression in the adult rat brain showed intense labeling in the hypothalamus, especially in the supraoptic and the paraventricular nuclei [11].
• Northern blot analyses of type I and type II macrophage scavenger receptors (type I and type II MSR) demonstrated that the mRNA levels of JO21b cells were lower than those of J774 cells [13].
• Further analysis by Western blot identified the MSR as the primary receptor for denatured type I collagen among Mphi; proteins purified from a heat-denatured type I collagen affinity column [14].
• MSR, but not MAMA, mRNA levels were increased after treatment with interleukin-1 alpha [12].

References