PMID- 16778071 OWN - NLM STAT- MEDLINE DCOM- 20061129 LR - 20200930 IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 291 IP - 5 DP - 2006 Nov TI - Oxygen availability regulates metabolism and gene expression in trout hepatocyte cultures. PG - R1507-15 AB - We studied the metabolic rate, cellular energetic state, hypoxia-inducible factor-1 (HIF-1) activation, and expression of enzymes involved in energy metabolism using rainbow trout (Oncorhynchus mykiss) hepatocytes over the oxygen range from 21 to 1 kPa. Oxygen dependence of these factors was assessed by gradually reducing oxygen supply to cells from 21 kPa to 10, 5, 2, and 1 kPa. Moreover, time course experiments for up to 20 h at oxygen tensions of 1 and 2 kPa were carried out. Reduction of oxygen from 21 kPa to 10, 5, 2, and 1 kPa decreased metabolic rate of the cells by 14, 24, 37, and 46%, respectively. This response was instantaneous and fully reversible upon reoxygenation. Cellular ATP content and the expression of all mRNAs studied decreased when oxygen was reduced from 21 to 5 and 2 kPa. The lowest ATP levels, approximately 43% of the initial value, were measured at 5 kPa of oxygen, whereas the reduction in mRNA amounts was most pronounced at 2 kPa. At 1 kPa oxygen tension, both ATP content and mRNA amounts returned to normoxic (21 kPa) levels with a concomitant activation of HIF-1, indicating reorganization of energy metabolism in adaptation of cells to low oxygen supply. These results show that oxygen has a direct regulatory effect on metabolism of trout hepatocyte cultures, supporting the view that oxygen has a profound role in metabolic regulation in cells. FAU - Rissanen, Eeva AU - Rissanen E AD - Centre of Excellence in Evolutionary Genetics and Physiology, Dept. of Biology, Univ. of Turku, FIN-20014, Turku, Finland. eeva.rissanen@utu.fi FAU - Tranberg, Hanna K AU - Tranberg HK FAU - Nikinmaa, Mikko AU - Nikinmaa M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060615 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Actins) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (RNA, Messenger) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 2.7.1.2 (Glucokinase) RN - EC 2.7.1.40 (Pyruvate Kinase) RN - S88TT14065 (Oxygen) SB - IM MH - Actins/genetics/metabolism MH - Adenosine Triphosphate/genetics/metabolism MH - Animals MH - Basal Metabolism/physiology MH - Cell Survival/physiology MH - Cells, Cultured MH - Energy Metabolism/physiology MH - Gene Expression Regulation/*physiology MH - Glucokinase/genetics/metabolism MH - Hepatocytes/cytology/*metabolism MH - Hypoxia-Inducible Factor 1/genetics/metabolism MH - Metabolism/*physiology MH - Oncorhynchus mykiss/genetics/physiology MH - Oxygen/*physiology MH - Pyruvate Kinase/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Time Factors EDAT- 2006/06/17 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/06/17 09:00 PHST- 2006/06/17 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/06/17 09:00 [entrez] AID - 00025.2006 [pii] AID - 10.1152/ajpregu.00025.2006 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1507-15. doi: 10.1152/ajpregu.00025.2006. Epub 2006 Jun 15.