This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pettersen, E. O. Articles by Rønning, O. W. Search for Related Content PubMed PubMed Citation Articles by Pettersen, E. O. Articles by Rønning, O. W.

Regulation of Protein Metabolism of Human Cells during and after Acute Hypoxia¹

Department of Tissue Culture, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo 3, Norway

Protein synthesis and protein degradation were measured in human NHIK 3025 cells cultured in vitro during and after an acute treatment of extreme hypoxia (<4 ppm O₂). Furthermore, total protein content per cell was recorded and related to cell cycle phase by coincident measurement of DNA and protein using two-parametric flow cytometry. During hypoxia protein synthesis was reduced and protein degradation was increased, resulting in no net accumulation of protein.

From the flow cytometric recordings, the amount of protein per cell was found to be constant, or perhaps in some of the cells slightly reduced, after a 3-h period of extreme hypoxia. Three h after reaeration protein degradation had returned to normal while protein synthesis was slightly above normal. The flow cytometric recordings showed that after reaeration the protein accumulation was particularly high in the subpopulation of cells which accumulated at the G₁-S border during hypoxia and entered S phase as a partly synchronized subpopulation after reaeration. Since we know from our earlier studies that these cells are more resistant to hypoxia than cells in S phase we conclude that this high protein accumulation may be important in restoring a pool of proteins which initiate DNA synthesis and perhaps other proteins of importance to cell growth.

¹ Supported by grants from the Norwegian Cancer Society.

² To whom requests for reprints should be addressed.

³ Fellow of the Norwegian Cancer Society.

Received 2/18/86. Revised 5/19/86. Accepted 5/21/86.

This article has been cited by other articles:

				R. M. Young, S.-J. Wang, J. D. Gordan, X. Ji, S. A. Liebhaber, and M. C. Simon Hypoxia-mediated Selective mRNA Translation by an Internal Ribosome Entry Site-independent Mechanism J. Biol. Chem., June 13, 2008; 283(24): 16309 - 16319. [Abstract] [Full Text] [PDF]

				J. D. Blais, C. L. Addison, R. Edge, T. Falls, H. Zhao, K. Wary, C. Koumenis, H. P. Harding, D. Ron, M. Holcik, et al. Perk-Dependent Translational Regulation Promotes Tumor Cell Adaptation and Angiogenesis in Response to Hypoxic Stress Mol. Cell. Biol., December 15, 2006; 26(24): 9517 - 9532. [Abstract] [Full Text] [PDF]

				F. Kaper, N. Dornhoefer, and A. J. Giaccia Mutations in the PI3K/PTEN/TSC2 Pathway Contribute to Mammalian Target of Rapamycin Activity and Increased Translation under Hypoxic Conditions Cancer Res., February 1, 2006; 66(3): 1561 - 1569. [Abstract] [Full Text] [PDF]

				I. Ernens, S. J. Goodfellow, F. Innes, N. S. Kenneth, L. E. Derblay, R. J. White, and P. H. Scott Hypoxic stress suppresses RNA polymerase III recruitment and tRNA gene transcription in cardiomyocytes Nucleic Acids Res., January 10, 2006; 34(1): 286 - 294. [Abstract] [Full Text] [PDF]

				H. Y. Yeung, K. P. Lai, H. Y. Chan, N. K. Mak, G. F. Wagner, and C. K. C. Wong Hypoxia-Inducible Factor-1-Mediated Activation of Stanniocalcin-1 in Human Cancer Cells Endocrinology, November 1, 2005; 146(11): 4951 - 4960. [Abstract] [Full Text] [PDF]

				J. D. Blais, V. Filipenko, M. Bi, H. P. Harding, D. Ron, C. Koumenis, B. G. Wouters, and J. C. Bell Activating Transcription Factor 4 Is Translationally Regulated by Hypoxic Stress Mol. Cell. Biol., September 1, 2004; 24(17): 7469 - 7482. [Abstract] [Full Text] [PDF]

				C. Koumenis, C. Naczki, M. Koritzinsky, S. Rastani, A. Diehl, N. Sonenberg, A. Koromilas, and B. G. Wouters Regulation of Protein Synthesis by Hypoxia via Activation of the Endoplasmic Reticulum Kinase PERK and Phosphorylation of the Translation Initiation Factor eIF2{alpha} Mol. Cell. Biol., November 1, 2002; 22(21): 7405 - 7416. [Abstract] [Full Text] [PDF]

				J. Yuan, L. Narayanan, S. Rockwell, and P. M. Glazer Diminished DNA Repair and Elevated Mutagenesis in Mammalian Cells Exposed to Hypoxia and Low pH Cancer Res., August 1, 2000; 60(16): 4372 - 4376. [Abstract] [Full Text]

				A. J. Giaccia and M. B. Kastan The complexity of p53 modulation: emerging patterns from divergent signals Genes & Dev., October 1, 1998; 12(19): 2973 - 2983. [Full Text]