The Response of Renal Tubular Epithelial Cells to Physiologically and Chemically Induced Growth Arrest

Jeongmi K Jeong,Qihong Huang,Serrine S Lau,Terrence J Monks

doi:10.1074/jbc.272.11.7511

Jeongmi K Jeong, Qihong Huang + Show 2 more

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https://doi.org/10.1074/jbc.272.11.7511

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Abstract

Cells respond to a variety of stresses by activating the transcription of a battery of "acute phase" or "stress response" genes. The nature of this response is tailored to the nature of the stress. The extent to which physiologically and pathophysiologically induced growth arrest share common genomic responses is unclear. We therefore compared the effects of a physiologically induced (serum and nutrient depletion) and a chemically induced (2-Br-bis-(GSyl)HQ and 2-Br-6-(GSyl)HQ) stress in renal tubular epithelial cells (LLC-PK1). The response to physiological stress, induced by serum depletion, involves growth arrest characterized by an inhibition of DNA synthesis that occurs in the absence of a decrease in histone mRNA or an increase in gadd153 mRNA, one of the growth arrest and DNA damage inducible genes. In contrast, the chemical-induced stress involves growth arrest accompanied by a decrease in histone mRNA, particularly core histone H2B and H2A mRNA, and the induction of gadd153. Chemical-induced changes in histone mRNA inversely correlate to changes in the expression of a stress gene, hsp70, whose expression is dependent upon the maintenance of appropriate nucleosomal structure.

Highlights

Cells respond to a variety of stresses by activating the transcription of a battery of “acute phase” or “stress response” genes [1, 2]
Nutrient Depletion-mediated Growth Arrest: Effects on the Growth Arrest and DNA Damage-inducible Gene, gadd153, and Histone mRNA in Renal Tubular Epithelial Cells—Depriving cells of serum and nutrients was sufficient to induce gadd153 expression (Fig. 1)
Because histone synthesis is tightly coupled to DNA synthesis, we examined the effects of this physiologically induced state of growth arrest on the expression of histone mRNA

Summary

Introduction

Cells respond to a variety of stresses by activating the transcription of a battery of “acute phase” or “stress response” genes [1, 2]. The nature of this response is tailored to the nature of the stress. We have compared physiologically induced (serum and nutrient depletion) and chemically induced (2-Br-bis-(GSyl)HQ and 2-Br-6-(GSyl)HQ) growth arrest in renal tubular epithelial cells (LLC-PK1) and determined some of the factors involved in regulating gene expression in response to the chemically induced stress. The chemically induced stress involves growth arrest accompanied by a decrease in histone mRNA, core histone H2A and H2B mRNA, and the induction of gadd153

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