scholarly journals Induction of heme oxygenase-1 and heat shock protein 70 in rat hepatocytes: The role of calcium signaling

2007 ◽  
Vol 12 (1) ◽  
Author(s):  
Malte Silomon ◽  
Inge Bauer ◽  
Michael Bauer ◽  
Julia Nolting ◽  
Markus Paxian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Heat Shock ◽  
Heme Oxygenase ◽  
Rat Hepatocytes ◽  
Glutathione Depletion ◽  
Heme Oxygenase 1 ◽  
Hsp70 Gene ◽  
Stress Response Genes

AbstractStress response genes including heat shock proteins are induced under a variety of conditions to confer cellular protection. This study investigated the role of calcium signaling in the induction of two stress response genes, heme oxygenase-1/hsp32 and hsp70, in isolated rat hepatocytes. Both genes were induced by cellular glutathione depletion. This induction could be inhibited by BAPTA-AM. Culturing in a calcium-free medium prevented the induction of hsp70 gene expression after glutathione depletion without affecting heme oxygenase-1 gene expression. Thapsigargin increased the gene expression of heme oxygenase-1 but not that of hsp70. Thapsigargin-induced heme oxygenase-1 induction was completely inhibited by BAPTA-AM. Incubation with the Ca2+-ionophore A23187 augmented heme oxygenase-1 (two-fold) and hsp70 (5.2-fold) mRNA levels. Our data suggests a significant role of Ca2+-dependent pathways in the induction of the two stress genes. An increase in the cytoplasmic Ca2+ activity seems to play a key role in the cascade of signaling leading to the induction of the two genes. However, the source of Ca2+ that fluxes into the cytoplasm seems to be different. Our data provides evidence for a compartmentalization of calcium fluxes, i.e. the Ca2+ flux from intracellular stores (e.g. the endoplasmic reticulum) plays a major role in the induction of heme oxygenase-1. By contrast, Ca2+ flux from the extracellular medium seems to be a mechanism initiating the cellular signaling cascade leading to hsp70 gene induction.

The possible role of heat shock factor-1 in the negative regulation of heme oxygenase-1

2005 ◽  
Vol 37 (3) ◽  
pp. 604-615 ◽  
Author(s):  
Yenn-Hwei Chou ◽  
Feng-Ming Ho ◽  
Der-Zen Liu ◽  
Shyr-Yi Lin ◽  
Li-Hsueh Tsai ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heme Oxygenase ◽  
Heat Shock Factor ◽  
Negative Regulation ◽  
Heme Oxygenase 1 ◽  
Heat Shock Factor 1

scholarly journals Regulation of human heme oxygenase-1 gene expression under thermal stress

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 5074-5084 ◽  
Author(s):  
S Okinaga ◽  
K Takahashi ◽  
K Takeda ◽  
M Yoshizawa ◽  
H Fujita ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thermal Stress ◽  
Heat Shock ◽  
Transient Expression ◽  
Reporter Gene ◽  
Heme Oxygenase ◽  
Gene Promoter ◽  
Heme Oxygenase 1 ◽  
Heat Shock Element ◽  
Hsp70 Mrna

Heme oxygenase-1 is an essential enzyme in heme catabolism, and its human gene promoter contains a putative heat shock element (HHO-HSE). This study was designed to analyze the regulation of human heme oxygenase-1 gene expression under thermal stress. The amounts of heme oxygenase-1 protein were not increased by heat shock (incubation at 42 degrees C) in human alveolar macrophages and in a human erythroblastic cell line, YN-1–0-A, whereas heat shock protein 70 (HSP70) was noticeably induced. However, heat shock factor does bind in vitro to HHO-HSE and the synthetic HHO-HSE by itself is sufficient to confer the increase in the transient expression of a reporter gene upon heat shock. The deletion of the sequence, located downstream from HHO-HSE, resulted in the activation of a reporter gene by heat shock. These results suggest that HHO-HSE is potentially functional but is repressed in vivo. Interestingly, heat shock abolished the remarkable increase in the levels of heme oxygenase-1 mRNA in YN-1–0-A cells treated with hemin or cadmium, in which HSP70 mRNA was noticeably induced. Furthermore, transient expression assays showed that heat shock inhibits the cadmium-mediated activation of the heme oxygenase-1 promoter, whereas the HSP70 gene promoter was activated upon heat shock. Such regulation of heme oxygenase-1 under thermal stress may be of physiologic significance in erythroid cells.

scholarly journals Heme Oxygenase-1 at the Nexus of Endothelial Cell Fate Decision Under Oxidative Stress

2021 ◽  
Vol 9 ◽  
Author(s):  
Sindhushree Raghunandan ◽  
Srinivasan Ramachandran ◽  
Eugene Ke ◽  
Yifei Miao ◽  
Ratnesh Lal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Stress Response ◽  
Cell Surface ◽  
Cell Survival ◽  
Cell Fate ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Cell Fate Decisions

Endothelial cells (ECs) form the inner lining of blood vessels and are central to sensing chemical perturbations that can lead to oxidative stress. The degree of stress is correlated with divergent phenotypes such as quiescence, cell death, or senescence. Each possible cell fate is relevant for a different aspect of endothelial function, and hence, the regulation of cell fate decisions is critically important in maintaining vascular health. This study examined the oxidative stress response (OSR) in human ECs at the boundary of cell survival and death through longitudinal measurements, including cellular, gene expression, and perturbation measurements. 0.5 mM hydrogen peroxide (HP) produced significant oxidative stress, placed the cell at this junction, and provided a model to study the effectors of cell fate. The use of systematic perturbations and high-throughput measurements provide insights into multiple regimes of the stress response. Using a systems approach, we decipher molecular mechanisms across these regimes. Significantly, our study shows that heme oxygenase-1 (HMOX1) acts as a gatekeeper of cell fate decisions. Specifically, HP treatment of HMOX1 knockdown cells reversed the gene expression of about 51% of 2,892 differentially expressed genes when treated with HP alone, affecting a variety of cellular processes, including anti-oxidant response, inflammation, DNA injury and repair, cell cycle and growth, mitochondrial stress, metabolic stress, and autophagy. Further analysis revealed that these switched genes were highly enriched in three spatial locations viz., cell surface, mitochondria, and nucleus. In particular, it revealed the novel roles of HMOX1 on cell surface receptors EGFR and IGFR, mitochondrial ETCs (MTND3, MTATP6), and epigenetic regulation through chromatin modifiers (KDM6A, RBBP5, and PPM1D) and long non-coding RNA (lncRNAs) in orchestrating the cell fate at the boundary of cell survival and death. These novel aspects suggest that HMOX1 can influence transcriptional and epigenetic modulations to orchestrate OSR affecting cell fate decisions.

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