Concomitant Nrf2- and ATF4-activation by Carnosic Acid Cooperatively Induces Expression of Cytoprotective Genes

Autor: Nobuhiko Harada, Ken Itoh, Seiichi Oyadomari, Randal J. Kaufman, Hiromi Yamazaki, Shusuke Taniuchi, Hidemi Yoshida, Junsei Mimura, Kunio Kosaka, Shuya Kasai, Atsushi Inose-Maruyama
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Aldo-Keto Reductases
Antioxidants
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Nerve Growth Factor
Gene expression
ATF4
lcsh:QH301-705.5
Spectroscopy
Regulation of gene expression
NGF
0303 health sciences
Chemistry
Tunicamycin
General Medicine
3. Good health
Computer Science Applications
Cell biology
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
Antioxidant
Signal Transduction
NF-E2-Related Factor 2
Activating Transcription Factor 4
Models
Biological
Article
Catalysis
Nrf2
Inorganic Chemistry
03 medical and health sciences
Aldehyde Reductase
Stress
Physiological
Cell Line
Tumor
Humans
Physical and Theoretical Chemistry
Carnosic acid
Molecular Biology
Transcription factor
030304 developmental biology
Activator (genetics)
Organic Chemistry
Hydroquinones
Nerve growth factor
lcsh:Biology (General)
lcsh:QD1-999
Gene Expression Regulation
Cytoprotection
Abietanes
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 7
International Journal of Molecular Sciences, Vol 20, Iss 7, p 1706 (2019)
ISSN: 1422-0067
DOI: 10.3390/ijms20071706
Popis: Carnosic acid (CA) is a phytochemical found in some dietary herbs, such as Rosmarinus officinalis L., and possesses antioxidative and anti-microbial properties. We previously demonstrated that CA functions as an activator of nuclear factor, erythroid 2 (NF-E2)-related factor 2 (Nrf2), an oxidative stress-responsive transcription factor in human and rodent cells. CA enhances the expression of nerve growth factor (NGF) and antioxidant genes, such as HO-1 in an Nrf2-dependent manner in U373MG human astrocytoma cells. However, CA also induces NGF gene expression in an Nrf2-independent manner, since 50 &mu
M of CA administration showed striking NGF gene induction compared with the classical Nrf2 inducer tert-butylhydroquinone (tBHQ) in U373MG cells. By comparative transcriptome analysis, we found that CA activates activating transcription factor 4 (ATF4) in addition to Nrf2 at high doses. CA activated ATF4 in phospho-eIF2&alpha
and heme-regulated inhibitor kinase (HRI)-dependent manners, indicating that CA activates ATF4 through the integrated stress response (ISR) pathway. Furthermore, CA activated Nrf2 and ATF4 cooperatively enhanced the expression of NGF and many antioxidant genes while acting independently to certain client genes. Taken together, these results represent a novel mechanism of CA-mediated gene regulation evoked by Nrf2 and ATF4 cooperation.
Databáze: OpenAIRE
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