Abstract:
:The antioxidant-activated transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the induction of cytoprotective genes against chemical toxicity and oxidative injuries. The role of phosphorylation in Nrf2 activation has been suggested but remains elusive. We report that phenolic antioxidant/pro-oxidant tert-butylhydroquinone (tBHQ) induced two forms of the Nrf2 protein in neuroblastoma cells (IMR-32), which migrated as distinctive bands on SDS-PAGE. In vitro treatment with lambda phosphatase eliminated the slower migrating form and increased the amount of the faster migrating form of Nrf2. In vivo (32)Pi-phosphorylation resulted in (32)Pi-labeling of the Nrf2 protein in the presence of tBHQ that can be dephosphorylated by lambda phosphotase, indicating that the slower migrating form is a phosphorylated Nrf2 protein and the faster form an unphosphorylated Nrf2. Unphosphorylated Nrf2 predominated in the cytoplasm, whereas the phosphorylated form preferentially localized in the nucleus. Nuclear Nrf2 can be dephosphorylated by lambda phosphotase in vitro and be converted to the faster migrating form, implicating phosphorylation of Nrf2 in the cytoplasmic-nuclear translocation of the protein. Deletional analyses from both the carboxyl- and amino-ends revealed the transcription activation (TA) domains Neh4 (Nrf2-ECH homology 4) and Neh5 (Nrf2-ECH homology 5) as a major region necessary for the phosphorylation. The TA domains are characterized by the presence of multiple phosphorylation sites of casein kinase 2 (CK2). Moreover, CK2 phosphorylated the TA domains in vitro. Treatment with CK2 inhibitor 2-dimethylamino-4,5,6,7,-tetrabromo-1H-benzimidazole (DMAT) blocked the induction of endogenous target genes of Nrf2 in cells and inhibited the TA activities of both the full length and the TA domains of Nrf2 to a large extent. Finally, phosphorylation of the TA domains correlated with the nuclear translocation of Nrf2 that was inhibited by DMAT in a concentration-dependent manner. The findings demonstrated that phosphorylation of Nrf2 at the TA domains by CK2 is an integral component of Nrf2 activation necessary for the nuclear localization and transcription activation function of Nrf2 in neuroblastoma cells.
journal_name
J Biochem Mol Toxicoljournal_title
Journal of biochemical and molecular toxicologyauthors
Apopa PL,He X,Ma Qdoi
10.1002/jbt.20212subject
Has Abstractpub_date
2008-02-01 00:00:00pages
63-76issue
1eissn
1095-6670issn
1099-0461journal_volume
22pub_type
杂志文章abstract::The early research found that the spiderlings of black widow spider (Latrodectus tredecimguttatus) exhibited obvious toxicity to animals. The present work performed a systematical analysis of the aqueous extract of newborn black widow spiderlings. The extract was shown to contain 69.42% of proteins varying in molecula...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21553
更新日期:2014-05-01 00:00:00
abstract::Certain ginsenosides, also known as triterpene glycosides, have been recently reported to have a characteristic effect on cultured intestinal and leukemia cell growth. Ginsenoside aglycones 20(S)-protopanaxadiol (PD), 20(S)-protopanaxatriol (PT), and ginsenoside Rh2 have been identified as having a strong effect on re...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.20019
更新日期:2004-01-01 00:00:00
abstract::Mitochondria play an important role in myocardial tissue homeostasis; therefore, deterioration in mitochondrial function will eventually lead to cardiomyocyte and endothelial cell death and consequently cardiovascular dysfunction. Lithium (Li+ ) is an effective drug for bipolar disorder with known cardiotoxic side eff...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21836
更新日期:2017-02-01 00:00:00
abstract::The aim of this study was to determine the antigenotoxic potential of two newly synthesized β-aminoketones against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 9-aminoacridine (9-AA)-induced mutagenesis. The mutant bacterial tester strains were MNNG-sensitive Escherichia coli WP2 uvrA and 9-AA-sensitive Salmonella ...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21414
更新日期:2012-07-01 00:00:00
abstract::The present study is the first attempt to report the characterization of a nucleotidase from Cerastes cerastes venom. A 70 kDa 5'-nucleotidase (Cc-5'NTase) was purified to homogeneity. The amino acid sequence of Cc-5'NTase displayed high homology with many nucleotidases. Its activity was optimal at pH 7 with a specifi...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21885
更新日期:2017-05-01 00:00:00
abstract::We studied action of inorganic phosphate (P(i)) on toxic effects of Tl+ in isolated rat liver mitochondria. This is a convenient model to study the toxicity of heavy metals. P(i) markedly retarded contraction of energized mitochondria swollen in the TlNO3 medium and even stronger stimulated swelling and state 4 of suc...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.20215
更新日期:2008-05-01 00:00:00
abstract::Cisplatin is a highly cytotoxic anticarcinogenic drug used to treat several kinds of solid tumors such as liver tumors. With the increase in the incidences associated with hepatic tumors and a lack of selectivity of cisplatin to cancer cells, it is important to explore new therapeutic strategies against them. The pres...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.22722
更新日期:2021-01-23 00:00:00
abstract::The use of the cytotoxic antibiotic doxorubicin (DOXR) is limited by its dose-dependent cardiotoxicity. The aim of this study was to evaluate the cardioprotective effect of the combination of carvedilol (CARD) and liposomal resveratrol (LIPO RESV) against DOXR-induced cardiomyopathy in rats. The results of the present...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.22492
更新日期:2020-07-01 00:00:00
abstract::Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diab...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.20317
更新日期:2010-03-01 00:00:00
abstract::Taxane-based chemotherapy drugs (cabazitaxel, docetaxel, and paclitaxel) are microtubule inhibitors, which are effectively and frequently used to treat metastatic prostate cancer (PCa). Among these, cabazitaxel is offered as a new therapeutic option for patients with metastatic castration-resistant PC as that are resi...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.22542
更新日期:2020-06-24 00:00:00
abstract::Garlic has been used as a traditional medicine to treat various diseases. Garlic reduces the risk of some diseases. This protective effect is due to the organosulfur compounds of garlic. The aim of this study was to investigate the inhibition effects of garlic-derived compounds on human immunodeficiency virus type 1 (...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.22215
更新日期:2018-11-01 00:00:00
abstract::Alkaline phosphatase (ALP) activity in the serum and liver from rats administered with cadmium (Cd) in drinking water was studied. After metal administration, Cd showed a time-dependent accumulation in the liver, meanwhile metallothionein had a maximum increase at 1 month, remaining in this level until the end of the ...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21732
更新日期:2015-12-01 00:00:00
abstract::The modulatory effect of taurine on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats was studied. DMBA (25 mg/kg body weight) was administered to induce breast cancer in rats. Protein carbonyl levels, activities of membrane bound enzymes (Na(+) /K(+) ATPase, Ca(2+) ATPase, and Mg(2+) ATPase), phase ...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21805
更新日期:2016-08-01 00:00:00
abstract::A full-length cDNA clone encoding a novel form of the cytochrome P450 3A subfamily (Cyp3a-25) has been isolated from a mouse liver cDNA library. The sequence contained 2010 base pairs and encoded a protein with 503 amino acids. The amino acid sequence shared greater identities with rat CYP3A18 (90%) and golden hamster...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.4
更新日期:2001-01-01 00:00:00
abstract::Limited research has been performed on S-adenosylhomocysteine (SAH) or homocysteine (Hcy)-evoked cell damage in hepatic and neuronal cells. In this study, we assessed effects of SAH or Hcy on cell cytotoxicity and DNA damage in hepatic and neuronal cells and attempted to find the underlying mechanism. Cell cytotoxicit...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.20298
更新日期:2009-09-01 00:00:00
abstract::Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm with high rate of lymph node metastasis and recurrence. The aim of this study is to evaluate the expression profile of T Lymphoma Invasion and Metastasis 1 (TIAM1) in OSCC and its correlation with clinical outcomes including lymph node metastasi...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21875
更新日期:2017-04-01 00:00:00
abstract::Recent studies have established the importance of estrogen-related receptor γ (ERRγ) as a required participant for insulin secretion in pancreatic β cells. Key downstream genes of ERRγ remain unclear in the pancreatic β cell. To understand the molecular role of ERRγ and elucidate potential key candidate genes involved...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.22390
更新日期:2019-10-01 00:00:00
abstract::c-Myc and vascular endothelial growth factor (VEGF) genes are frequently deregulated and overexpressed in this malignancy, and strategies designed to inhibit c-Myc and VEGF expression in cancer cells may have considerable therapeutic value. In the present study, we design and use short interfering RNA (siRNA) to inhib...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21455
更新日期:2012-12-01 00:00:00
abstract::Uroporphyrinogen decarboxylase is an essential enzyme in all organisms and functions in the heme biosynthetic pathway, catalyzing the decarboxylation of the four acetate groups of uroporphyrinogen to form coproporphyrinogen. This work examines whether the four sequential decarboxylations occur at the same active site,...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.20055
更新日期:2005-01-01 00:00:00
abstract::The main topic of this study was to investigate the effect of benzo[a]pyrene (BP) on microRNAs and their target genes expression levels in primary cell cultures from normal and malignant endometrial tissue. MicroRNA-126 (miR-126) and miR-190a were most sensitive to BP treatment. The treatment of both cultures with BP ...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.22314
更新日期:2019-06-01 00:00:00
abstract::The action of carbenoxolone on hepatic energy metabolism was investigated in the perfused rat liver and isolated mitochondria. In perfused livers, carbenoxolone (200-300 microM) increased oxygen consumption, glucose production and glycolysis from endogenous glycogen. Gluconeogenesis from lactate or fructose, an energy...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.20139
更新日期:2006-01-01 00:00:00
abstract::The present study was designed to elucidate the involvement of acid phosphatase (ACP) in metastasis and lactate dehydrogenase (LDH) as an immediate compensatory alleviation mechanism for energy stress in liver lesions induced by hexachlorocyclohexane in Swiss mice. Animals were continuously exposed to hexachlorocycloh...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21441
更新日期:2012-11-01 00:00:00
abstract::It has been reported that the bioactive intermediate metabolites of trazodone might cause hepatotoxicity. This study was designed to investigate the exact mechanism of hepatocellular injury induced by trazodone as well as the protective effects of taurine and/or melatonin against this toxicity. Freshly isolated rat he...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21509
更新日期:2013-10-01 00:00:00
abstract::Hepatotoxicants can elicit liver damage by various mechanisms that can result in cell necrosis and death. The changes induced by these compounds can vary from gross alterations in DNA repair mechanisms, protein synthesis, and apoptosis, to more discrete changes in oxidative damage and lipid peroxidation. However, litt...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/1099-0461(2000)14:5<283::AID-JBT7>3.0.CO;2
更新日期:2000-01-01 00:00:00
abstract::In the current study, neuroprotective significance of ellagic acid (EA, a polyohenol) was explored by primarily studying its antioxidant and antiapoptotic potential against arsenic trioxide (As2 O3 )-induced toxicity in SH-SY5Y human neuroblastoma cell lines. The mitigatory effects of EA with particular reference to c...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.22024
更新日期:2018-02-01 00:00:00
abstract::Habitual consumption of some Melanesian medicinal and food plants may influence atherosclerosis development via their antioxidant capacity at the endothelial level. Areca nut (AN; Areca catechu), piper inflorescence (PBI; Piper betle), betel quid (BQ), guava buds (GB; Psidium guajava), the leaves (NL), juice (NJ), fru...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.20186
更新日期:2007-01-01 00:00:00
abstract::The quantitative influence of copper on the interaction between cytochrome c and sulfite, which is a derivate of sulfur dioxide in the human body, has been studied by fluorescence spectrometry and ultraviolet absorption spectrometry in vitro. The results indicate that copper may intensely combine with protein componen...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.20143
更新日期:2006-01-01 00:00:00
abstract::This study investigated the protective potential of Naringin (NIN) against cadmium chloride (CdCl2 ) mediated hepatotoxicity using human hepatocellular carcinoma (HepG2) cells. An optimal concentration of NIN (5 μM) was potent enough to confer cytoprotection against CdCl2 (50 μM) as was observed by MTT assay. Precondi...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21915
更新日期:2017-08-01 00:00:00
abstract::Colorectal cancer (CRC) is the leading type of diagnosed cancer; globally, it resides in the fourth-leading origin of cancer-interrelated mortality in the globe. The treatment strategies were chemotherapy and potent radiotherapy. Although chemotherapy treatment can eliminate tumor cells, it remains with unnecessary to...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.22665
更新日期:2020-12-28 00:00:00
abstract::The full-length sequence of the protein phosphatase 2A subunit A (PP2A-A) cDNA from silver carp was cloned and sequenced. Additionally, the transcription of PP2A-A in the liver, kidney, and spleen of fish after microcystin (MC)-exposure were also determined in this study. The results reveal that PP2A-A cDNA is 2833 ba...
journal_title:Journal of biochemical and molecular toxicology
pub_type: 杂志文章
doi:10.1002/jbt.21706
更新日期:2015-09-01 00:00:00