Disease relevance of AGPAT1

• 4. Human LPAAT-alpha and -beta isoforms were cloned and transfected into E. coli, demonstrating the ability to restore PA synthesis and reduce lyso-PA accumulation in plsC strains (LPAAT deficient mutants), as well as restoring growth at high temperatures [1].
• RESULTS:: Both G5 and G15 showed concurrent recovery of r-CBF and BrT with hyperemia and hyperthermia, respectively, 10 to 15 minutes after reperfusion [2].
• METHODS:: Eighteen Mongolian gerbils were assigned to one of three groups: 5-minute (G5), 15-minute (G15), or 30-minute (G30) ischemia [2].

High impact information on AGPAT1

• Here we show that the C-terminal extension of the enzyme is not required for the selection of G15 as the site of base exchange; truncated forms of Pyrococcus furiosus TGT retain their specificity for guanine exchange at position 15 [3].
• The present study in generation 15 (G15) female rats tested the hypothesis that continuing improvement in skeletal muscle O(2) transfer must be accompanied by augmentation in Qo(2 max) to support Vo(2 max) of HCR [4].
• The greater G15 Qo(2 max) of HCR was due to a 48% greater stroke volume than LCR [4].
• LPAAT-alpha mRNA was detected in all tissues with highest expression in skeletal muscle whereas LPAAT-beta was expressed predominantly in heart and liver tissues [5].
• These results explain the susceptibility of E. coli and the resistance of human Jurkat cells to G15, and may have implications in designing membrane-selective therapeutic agents [6].

Biological context of AGPAT1

• The LPAAT-alpha gene is located on chromosome 6p21.3, an area within the class III region of the major hiscompatibility complex (MHC) and the LPAAT-beta gene is mapped to chromosome 9q34 [7].
• LPAAT-alpha transfection increases linolenate incorporation into PA at the expense of linoleate incorporation, which is reversed by LSF [1].

Anatomical context of AGPAT1

• LPAAT-alpha mRNA is uniformly expressed throughout most tissues with the highest level found in skeletal muscle; whereas LPAAT-beta is differentially expressed, with the highest level found in heart and liver, and negligible level in brain and placenta [7].
• However, G15 does not bind to lipid vesicles made of POPC/POPG/Chl (9:1:1) mixture, mimicking tumor cell membrane [6].

Analytical, diagnostic and therapeutic context of AGPAT1

• We investigated the target membrane selectivity of G15 using fluorescence, circular dichroism and 31P NMR methods [6].

References