Nrf2-dependent gene expressions: a molecular toxicological aspect.

نویسندگان

  • Satoshi Numazawa
  • Takemi Yoshida
چکیده

Although NF-E2 related factor 2 (Nrf2) was found to be a transcriptional regulator that controls an expression of the beta-globin gene, the notion is now widely accepted that this transfactor serves as a master regulator for the gene expression of a battery of proteins acting on anti-oxidative stress and detoxification of electrophiles. The function of Nrf2 that bears transcriptional activation depends solely on its nuclear localization, which is regulated by interaction with the cytosolic anchor protein Keap1 and its own turnover rate. In the present mini-review, we focus on the regulation of Nrf2 function and discuss the physiological and toxicological aspects of this transcriptional factor.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Pau d'arco activates Nrf2-dependent gene expression via the MEK/ERK-pathway.

Pau d'arco is a plant-derived traditional medicine that acts by poorly understood molecular mechanisms. Here, we studied the effect of pau d'arco on the cytoprotective transcription factor Nrf2. An aqueous extract of pau d'arco stimulated Nrf2-dependent gene expression and led to nuclear localization of Nrf2 in vitro. Chromatographic separation and mass spectrometry of the extract identified be...

متن کامل

Enhanced 4-Hydroxynonenal Resistance in KEAP1 Silenced Human Colon Cancer Cells

Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense. The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus. In the present study, we aimed to investigate t...

متن کامل

Erk activation is required for Nrf2 nuclear localization during pyrrolidine dithiocarbamate induction of glutamate cysteine ligase modulatory gene expression in HepG2 cells.

Pyrrolidine dithiocarbamate (PDTC) induction of the human glutamate cysteine ligase modulatory (GCLM) gene is dependent on activation of the mitogen-activated protein kinases (MAPKs) extracellular regulated kinase (Erk) and p38, and is not affected by protein kinase C (PKC) or PI3K inhibitors. Nrf2 binding to the electrophile response element (EpRE) located within the GCLM promoter is decreased...

متن کامل

Protection against chromium (VI)-induced oxidative stress and apoptosis by Nrf2. Recruiting Nrf2 into the nucleus and disrupting the nuclear Nrf2/Keap1 association.

Chromium (Cr) (VI) is a major environmental toxic metal and a human carcinogen. The molecular events mediating cellular responses to Cr(VI) are not clear at present. We show that Cr(VI) potently induced apoptosis and production of reactive oxygen species (ROS) in mouse hepa1c1c7 cells in a concentration-dependent manner. Mouse embryonic fibroblast cells lacking Nrf2 exhibited elevated ROS produ...

متن کامل

Loss of Nrf2 in mice evokes a congenital intrahepatic shunt that alters hepatic oxygen and protein expression gradients and toxicity.

The transcription factor Nrf2 (Nfe2l2 nuclear factor, erythroid 2-like 2) regulates gene expression directly, controlling pharmacological and toxicological responses. These processes may also be influenced by the structure of the hepatic vasculature, which distributes blood flow through compartmentalized microenvironments to maintain organismal stability. Castings of the hepatic portal vasculat...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of toxicological sciences

دوره 29 2  شماره 

صفحات  -

تاریخ انتشار 2004