Overexpression of Ref-1 Inhibits Lead-induced Endothelial Cell Death via the Upregulation of Catalase

Lee, Kwon-Ho; Lee, Sang Ki; Kim, Hyo Shin; Cho, Eun Jung; Joo, Hee Kyoung; Lee, Eun Ji; Lee, Ji Young; Park, Myoung Soo; Chang, Seok Jong; Cho, Chung–Hyun; Park, Jin Bong; Jeon, Byeong Hwa

doi:10.4196/kjpp.2009.13.6.431

Cited by 8 publications

(3 citation statements)

References 37 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the cell type used in our study is different from theirs and our lead exposure time (26 days) is much longer than theirs (48 h), the high concentration of lead (30 lM) used in our study is far below their level. In fact, lead-30 lM or higher is the most widely used concentration for investigating the mechanism of lead toxicity in vitro (Lee et al, 2009;Robinson et al, 2015;Zheng et al, 1999).…”

Section: Methodsmentioning

confidence: 99%

RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations

Jiang

Hou

Bolin

et al. 2017

Toxicological Sciences

View full text Add to dashboard Cite

Lead (Pb) is a well-known toxicant, especially for the developing nervous system, albeit the mechanism is largely unknown. In this study, we use time series RNA-seq to conduct a genome-wide survey of the transcriptome response of human embryonic stem cell-derived neural progenitor cells to lead treatment. Using a dynamic time warping algorithm coupled with statistical tests, we find that lead can either accelerate or decelerate the expression of specific genes during the time series. We further show that lead disrupts a neuron- and brain-specific splicing factor NOVA1 regulated splicing network. Using lead induced transcriptome change signatures, we predict several known and novel disease risks under lead exposure. The findings in this study will allow a better understanding of the mechanism of lead toxicity, facilitate the development of diagnostic biomarkers and treatment for lead exposure, and comprise a highly valuable resource for environmental toxicology. Our study also demonstrates that a human (embryonic stem) cell-derived system can be used for studying the mechanism of toxicants, which can be useful for drug or compound toxicity screens and safety assessment.

show abstract

Section: Methodsmentioning

confidence: 99%

RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations

Jiang

Hou

Bolin

et al. 2017

Toxicological Sciences

View full text Add to dashboard Cite

show abstract

“…Additionally, increased nicotinamide adenine dinucleotide phosphate oxidase activity [7] and down-regulated expression of catalase [8] have also been shown to contribute to Pb-induced hypertension. Pb poisoning affects the hematopoietic system, inducing anemia by the unusual mechanism of rapid red blood cell destruction, as well as by inhibiting hemoglobin synthesis [9,10].…”

Section: Introductionmentioning

confidence: 99%

Korean Red Ginseng Protects Oxidative Injury Caused by Lead Poisoning

Park¹,

Cho²,

Lee³

et al. 2010

Journal of Ginseng Research

View full text Add to dashboard Cite

“…The observation of an increased LH pool in response to Pb 2ϩ may have implications for the pathology of Pb 2ϩ toxicity. For instance, the increase in LH in response to Pb 2ϩ may contribute to a cytotoxic heme pool (5,6) that leads to the oxidative stress associated with Pb 2ϩ toxicity (76,77). Alternatively, given that there are a number of heme-regulated transcription factors, kinases, and ion channels (1, 2), the increase in LH in response to Pb 2ϩ may be required to activate heme-based signaling pathways important for adaptation to heavy metal stress.…”

Section: Stress-induced Heme Signalingmentioning

confidence: 99%

Heme bioavailability and signaling in response to stress in yeast cells

Hanna

Kim

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

Protoheme (hereafter referred to as heme) is an essential cellular cofactor and signaling molecule that is also potentially cytotoxic. To mitigate heme toxicity, heme synthesis and degradation are tightly coupled to heme utilization in order to limit the intracellular concentration of "free" heme. Such a model, however, would suggest that a readily accessible steady-state, bioavailable labile heme (LH) pool is not required for supporting heme-dependent processes. Using the yeast as a model and fluorescent heme sensors, site-specific heme chelators, and molecular genetic approaches, we found here that 1) yeast cells preferentially use LH in heme-depleted conditions; 2) sequestration of cytosolic LH suppresses heme signaling; and 3) lead (Pb) stress contributes to a decrease in total heme, but an increase in LH, which correlates with increased heme signaling. We also observed that the proteasome is involved in the regulation of the LH pool and that loss of proteasomal activity sensitizes cells to Pb effects on heme homeostasis. Overall, these findings suggest an important role for LH in supporting heme-dependent functions in yeast physiology.

show abstract

Overexpression of Ref-1 Inhibits Lead-induced Endothelial Cell Death via the Upregulation of Catalase

Cited by 8 publications

References 37 publications

RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations

RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations

Korean Red Ginseng Protects Oxidative Injury Caused by Lead Poisoning

Heme bioavailability and signaling in response to stress in yeast cells

Contact Info

Product

Resources

About