Differences in Biochemical Properties and in Biological Function between Human SP-A1 and SP-A2 Variants, and the Impact of Ozone-Induced Oxidation

Guirong Wang, Sandra R. Bates-Kenney, Jian Qin Tao, David Phelps, Joanna Floros

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Abstract

The human surfactant protein A (SP-A) locus consists of two functional genes, SP-A1 and SP-A2, with several alleles characterized for each gene. Functional variations between SP-A1 and SP-A2 variants either before or after ozone exposure have been observed. To understand the basis of these differences, we studied SP-A1 and SP-A2 variants by comparing coding sequences, oligomerization patterns under various conditions, composition of oligomers with regard to amino terminal sequence isoforms, biological activity (regulation of phosphatidylcholine (PC) secretion by alveolar type II cells), and the impact of ozone-induced oxidation. We found that (i) the SP-A1 (6A 4) allele is the most divergent from all SP-A2 alleles, particularly from the SP-A2 (1A1). (ii) Differences exist in oligomerization among SP-A1, SP-A2, and coexpressed SP-A1/SP-A2, with higher order multimers (i.e., consisting of more subunits) observed for SP-A1 than for SP-A2 variants. Differences among SP-A1 or SP-A2 gene products are minimal. (iii) Amino acid variants in the amino terminal sequences are observed after signal peptide removal, including variants with an extra cysteine. (iv) Oxidation is observed after ozone exposure, involving several SP-A residues that include cysteine, methionine, and tryptophan. (v) The SP-A2 variant (1A0) and the coexpressed protein 1A0/6A2 inhibit ATP-stimulated PC secretion from alveolar type II cells to a greater extent than SP-A1 (6A 2), a biologic activity that was susceptible to ozone treatment.

Original languageEnglish (US)
Pages (from-to)4227-4239
Number of pages13
JournalBiochemistry
Volume43
Issue number14
DOIs
StatePublished - Apr 13 2004

Fingerprint

Ozone
varespladib methyl
Pulmonary Surfactant-Associated Protein A
Oxidation
Oligomerization
Genes
Phosphatidylcholines
Cysteine
Alveolar Epithelial Cells
Protein Sorting Signals
Bioactivity
Oligomers
Tryptophan
Methionine
Alleles
Protein Isoforms
Adenosine Triphosphate
Amino Acids
Chemical analysis
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

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title = "Differences in Biochemical Properties and in Biological Function between Human SP-A1 and SP-A2 Variants, and the Impact of Ozone-Induced Oxidation",
abstract = "The human surfactant protein A (SP-A) locus consists of two functional genes, SP-A1 and SP-A2, with several alleles characterized for each gene. Functional variations between SP-A1 and SP-A2 variants either before or after ozone exposure have been observed. To understand the basis of these differences, we studied SP-A1 and SP-A2 variants by comparing coding sequences, oligomerization patterns under various conditions, composition of oligomers with regard to amino terminal sequence isoforms, biological activity (regulation of phosphatidylcholine (PC) secretion by alveolar type II cells), and the impact of ozone-induced oxidation. We found that (i) the SP-A1 (6A 4) allele is the most divergent from all SP-A2 alleles, particularly from the SP-A2 (1A1). (ii) Differences exist in oligomerization among SP-A1, SP-A2, and coexpressed SP-A1/SP-A2, with higher order multimers (i.e., consisting of more subunits) observed for SP-A1 than for SP-A2 variants. Differences among SP-A1 or SP-A2 gene products are minimal. (iii) Amino acid variants in the amino terminal sequences are observed after signal peptide removal, including variants with an extra cysteine. (iv) Oxidation is observed after ozone exposure, involving several SP-A residues that include cysteine, methionine, and tryptophan. (v) The SP-A2 variant (1A0) and the coexpressed protein 1A0/6A2 inhibit ATP-stimulated PC secretion from alveolar type II cells to a greater extent than SP-A1 (6A 2), a biologic activity that was susceptible to ozone treatment.",
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Differences in Biochemical Properties and in Biological Function between Human SP-A1 and SP-A2 Variants, and the Impact of Ozone-Induced Oxidation. / Wang, Guirong; Bates-Kenney, Sandra R.; Tao, Jian Qin; Phelps, David; Floros, Joanna.

In: Biochemistry, Vol. 43, No. 14, 13.04.2004, p. 4227-4239.

Research output: Contribution to journalArticle

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AU - Wang, Guirong

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