Fluid shear stress induction of the transcriptional activator c-fos in human and bovine endothelial cells, HeLa, and Chinese hamster ovary cells

The c‐fos protein belongs to a family of transcriptional cofactors that can complex with proteins of the Jun family and activate mRNA transcription from gene promoters containing an activator protein 1 (AP‐1) binding element. The shear stress inducibility of the c‐fos protein was studied in human and animal cell lines of vastly different origins. Primary human umbilical vein endothelial cells (HUVEC), bovine aortic endothelial cells (BAEC, passage 2–14), HeLa cells, and Chinese hamster ovary (CHO) cells were subjected to steady laminar shear stress using a parallel plate flow apparatus. After 1 h of flow exposure at 25 dyn/cm2, the c‐fos levels in nuclei of shear stress HUVEC, BAEC, HeLa, and CHO were 5.4 ± 2.0 (n = 3), 2.25 ± 1.38 (n = 6), 2.14 ± 0.07 (n = 8), 1.92 ± 0.58 (n = 2) times higher, respectively, than in matched stationary controls. Flow exposure at 4 dyn/cm2 caused no enhancement of c‐fos levels in any of the cell lines tested, but caused significant reduction in c‐fos expression in the HeLa cells. The c‐fos induction by shear stress could be blocked by pharmacological agents. For example, the flow induction of the c‐fos protein levels was blocked by 50% with the preincubation of HUVEC with a protein kinase C inhibitor, H7 (10 μM) and blocked completely in HeLa cells preincubated with the phospholipase C inhibitor, neomycin (5 mM). The minimum time of shear stress exposure required to induce the c‐fos protein expression in HeLa cells was found to be as low as 1 min. By Northern analysis, the c‐fos mRNA levels were found to be elevated in BAEC, CHO, and HeLa cells exposed to 25 dyn/cm2 for 30 min. These studies indicate that c‐fos induction is a consistent genetic response in a variety of mammalian cells that may alter cellular phenotype in mechanical environments. © 1996 John Wiley & Sons, Inc.