Osteopontin inhibits expression of cytochrome c oxidase in RAW 264.7 murine macrophages.
Osteopontin (OPN) functions as both a cell attachment protein and a cytokine that signals through two CAM molecules: alpha(v)beta(3)-integrin and CD44. OPN initiates a number of signal transduction pathways that control cell survival, proliferation, and migration. In this study, utilizing RAW 264.7 murine macrophages, we demonstrate that expression of the mitochondrial protein, CCOI, is significantly decreased in the setting of OPN stimulation. This effect is blocked by the CD44 competitive ligand, hylauronate; GRGDSP, a hexapeptide that blocks OPN-integrin binding, had no effect. CCOI mRNA and transcription were significantly decreased in the presence of OPN; CCOI mRNA half-life was unaltered by OPN. Additional mitochondrial run-on studies, which included genes from L-strand and H-strand, suggest that OPN terminates transcription of the distal H-strand. CCO enzyme activity was also significantly decreased by OPN. Our results indicate that OPN inhibits CCOI expression as the result of a novel CD44-dependent transcriptional regulatory mechanism of the mitochondrial H strand.
Gao
Chengjiang
C
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Guo
Hongtao
H
Wei
Junping
J
Kuo
Paul C
PC
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors*; D015723:Gene Library; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000378:metabolism; D015151:Immunoblotting; D008024:Ligands; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D053495:Osteopontin; D010455:Peptides / Q000737:chemistry; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic
D018076:DNA, Complementary; D018960:Hyaluronan Receptors; D008024:Ligands; D010455:Peptides; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D003576:Electron Transport Complex IV