Disease relevance of ELA2A

• METHODS: Recombinant ELA2A and ELA2B were expressed in Escherichia coli, and their activity was tested on Glt-Ala-Ala-Pro-Leu-p-nitroanilide, DQ elastin and bovine milk protein [1].
• This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock) characterized by high mortality rate (0% survival, 120 min following the release of clamps), a profound hypotension and vascular dysfunction consisting of a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) of aortic rings [2].

High impact information on ELA2A

• In vitro footprinting and quantitative gel shift analyses showed that PF1 binds preferentially to the PE1 element but also at lower affinity to two other AT-rich regions upstream of PE1 [3].
• We have isolated a rice cDNA clone (pR4) encoding a DNA binding protein that binds to the AT-rich PE1 element [3].
• Functional analysis of the oat PHYA3 promoter in a transfection assay has revealed two positive elements, PE1 and PE3, that function synergistically to support high levels of transcription in the absence of light [3].
• In contrast, chymotrypsin B, elastase 2A, or elastase 3A (proteinase E) are ineffective [4].
• The 100-base pair ELA1 transcriptional enhancer drives high level transcription to pancreatic acinar cells of transgenic mice and in transfected pancreatic acinar cells in culture [5].

Biological context of ELA2A

• Finally, chimeras and point mutations engineered between ELA2A and ELA2B revealed that multiple evolutionary mutations inactivated ELA2B [1].
• The binding domains of PE-1 and PE-2 have been broadly located, with respect to the primary translation product, within the amino acid sequences 152-207 and 84-131, respectively [6].
• USF recognition of the PE1/PE2 region E box sites required phosphorylation with several potential involved residues, including T153, maping to the USF-specific region (USR) [7].

Anatomical context of ELA2A

• CONCLUSIONS: The results indicate that ELA2B is not an elastase enzyme and confirm that ELA2A is the major elastase in the human pancreas [1].
• Immunoblot analysis of total bovine adrenomedullary chromaffin granule lysate reveals PE-1 and PE-2 immunoreactive forms of observed molecular mass 35, 33, 29, 24, 22, and 15 kDa, and an 18-kDa PE-1 immunoreactive form [6].

Associations of ELA2A with chemical compounds

• There is preliminary evidence that PE-1 may be detecting a subset of polypeptides where shortening from the NH2 terminus has occurred [6].
• Incorporation of vitamin E in PE1- to PE7-treated cells were significantly (P < 0.05) increased compared to controls and were comparable to each other [8].
• Mafosfamide-lysine, a stable cyclophosphamide congener, strongly inhibited primary colony formation (PE1) with a D10 value of 14.46 +/- 1.76 micrograms/ml, but was much less efficient in the PE2 assay [9].
• Moreover, melphalan was equally effective in inhibiting CFU-L growth in both PE1 and PE2 assays, with D10 values of 1.53 +/- 0.17 micrograms/ml and 1.59 +/- 0.21 micrograms/ml for PE1 and PE2, respectively (p = 0.48) [9].
• Vesnarinone suppressed the primary (PE1) and secondary (PE2) colony-formation of leukemic blast progenitors in six AML patients tested [10].

Other interactions of ELA2A

• RESULTS: Surprisingly, recombinant ELA2B was completely devoid of proteolytic activity, while ELA2A readily hydrolyzed all three test substrates [1].
• MCP-1 protein (ELISA) was elevated 21-fold and myeloperoxidase activity 95-fold in RV of PE2.0 compared with Veh or PE1 [11].
• The NH2-terminal 20-amino acid sequence shares 50-55% identity with human alpha-tryptase, elastase 2A and 2B, chymotrypsin, acrosin, and the catalytic chains of hepsin, plasma kallikrein, and coagulation factor XI [12].

References