Decreased expression of P-glycoprotein in interleukin-1β and interleukin-6 treated rat hepatocytes.pdfVIP

Furihata Genes and Environment (2015) 37:21 DOI 10.1186/s41021-015-0021-9 REVIEW Open Access An active alternative splicing isoform of human mitochondrial 8-oxoguanine DNA glycosylase (OGG1) Chie Furihata1,2 Abstract Eight alternatively spliced isoforms of human 8-oxoguanine DNA glycosylase (OGG1) (OGG1-1a, −1b, −1c, −2a, −2b, −2c, −2d and −2e) are registered at the National Center for Biotechnology Information (NCBI). OGG1-1a is present in the nucleus, whereas the other seven isoforms are present in the mitochondria. Recombinant OGG1-1a has been purified and enzyme kinetics determined. OGG1(s) in mitochondria have not been fully characterized biochemically until recently. The major mitochondrial OGG1 isoform, OGG1-2a (also named β-OGG1), has also been expressed and purified; however, its activity is unresolved. Recently, we purified recombinant mitochondrial OGG1-1b and found that it was an active OGG1 enzyme. We reported its enzyme kinetics and compared the results with those of OGG1-1a. The reaction rate constant of OGG1-1b 8-oxoG glycosylase activity (kg) was 8-oxoG:C 8-oxoG:T 8-oxoG:G 8-oxoG:A and was similar to that of OGG1-1a under single-turnover conditions ([E] [S]). Both OGG1-1b and OGG1-1a showed high specificity towards 8-oxoG:C. The reaction rate constant of OGG1-1b N-glycosylase/DNA lyase activity (kgl) was 8-oxoG:C 8-oxoG:T ≃ 8-oxoG:G 8-oxoG:A and that of OGG1-1a was 8-oxoG:C 8-oxoG:T, 8-oxoG:G and 8-oxoG:A. The kgl of OGG1-1b and OGG1-1a is one order of magnitude lower than the corresponding kg value. OGG1-1b showed an especially low kgl towards 8-oxoG:A. Comparable expression of OGG1-1a and OGG1-1b was detected by RT-PCR in normal human lung tissue and lung cell lines. These results suggest that OGG1-1b is associated with 8-oxoG cleavage in human lung mitochondria and tha