Induction of Heme Oxygenase-1 (HO-1) and NAD[P]H: Quinone Oxidoreductase 1 (NQO1) by a Phenolic Antioxidant, Butylated Hydroxyanisole (BHA) and Its Metabolite, tert-Butylhydroquinone (tBHQ) in Primary-Cultured Human and Rat Hepatocytes

Keum, Young‐Sam; Han, Yong‐Hae; Liew, Celine Valeria; Kim, Junghwan; Xu, Changjiang; Yuan, Xian‐You; Shakarjian, Michael P.; Chong, Samuel S.; Kong, Ah‐Ng Tony

doi:10.1007/s11095-006-9094-2

Cited by 83 publications

(64 citation statements)

References 38 publications

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“…Both HO-1 and NQO1 are up-regulated in response to oxidative stress through increased transcription (23). We have shown previously that Star-PAP and PIPKI␣ are required for the up-regulation of the HO-1 transcript in response to a tBHQ-induced antioxidant response by playing a direct role in the 3Ј-end formation of this mRNA (6).…”

Section: Resultsmentioning

confidence: 94%

CKIα Is Associated with and Phosphorylates Star-PAP and Is Also Required for Expression of Select Star-PAP Target Messenger RNAs

Gonzales

Mellman

Anderson

2008

Journal of Biological Chemistry

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We have recently identified Star-PAP, a nuclear poly(A) polymerase that associates with phosphatidylinositol-4-phosphate 5-kinase I␣ (PIPKI␣) and is required for the expression of a specific subset of mRNAs. Star-PAP activity is directly modulated by the PIPKI␣ product phosphatidylinositol 4,5-bisphosphate (PI-4,5-P 2 ), linking nuclear phosphoinositide signaling to gene expression. Here, we show that PI-4,5-P 2 -dependent protein kinase activity is also a part of the Star-PAP protein complex. We identify the PI-4,5-P 2 -sensitive casein kinase I␣ (CKI␣) as a protein kinase responsible for this activity and further show that CKI␣ is capable of directly phosphorylating Star-PAP. Both CKI␣ and PIPKI␣ are required for the synthesis of some but not all Star-PAP target mRNA, and like Star-PAP, CKI␣ is associated with these messages in vivo. Taken together, these data indicate that CKI␣, PIPKI␣, and Star-PAP function together to modulate the production of specific Star-PAP messages. The Star-PAP complex therefore represents a location where multiple signaling pathways converge to regulate the expression of specific mRNAs.Polyadenylation of most mRNAs is required for their efficient transcription and export as well as regulating their stability and translational efficiency (1). Polyadenylation of mRNA is achieved through the activity of poly(A) polymerases (PAPs). 2There are multiple PAPs in mammalian cells, including PAP␣, which is thought to be primarily responsible for the polyadenylation of newly transcribed mRNAs in the nucleus (2, 3). Additionally, there are "non-canonical" PAPs, including Gld2 and Trf4, which regulate stability and degradation of specific RNAs through polyadenylation (4, 5).Star-PAP is a non-canonical poly(A) polymerase that is distinct from all other currently characterized PAP enzymes (6). Like the canonical PAP␣, Star-PAP has an RNA recognition motif and is a nuclear enzyme. However, similar to non-canonical PAPs, the Star-PAP protein complex and architecture differ significantly from PAP␣, and consequently, Star-PAP specifically targets a select subset of mRNAs. This suggests that Star-PAP is a hybrid PAP that is required for the 3Ј-end formation of newly transcribed pre-mRNAs but functions in a regulatory role to control mRNA expression levels. Star-PAP has a unique domain structure relative to all other known PAPs (6). One unique feature is a 205-amino acid proline-rich region (PRR) inserted into the catalytic PAP core. The PRR splits the catalytic PAP domain, and this region represents a potential site for regulation of Star-PAP function.Poly(A) polymerases operate as large multiprotein complexes responsible for the 3Ј-processing of RNAs (7, 8). The Star-PAP polyadenylation complex is similar to that of poly(A) polymerases that utilizes mRNA as a substrate and includes cleavage and polyadenylation specificity factor (CPSF) subunits, cleavage stimulatory factor (CstF) subunits, symplekin, and RNA polymerase II (6, 9). However, unlike other poly(A) polymerase complexes, the Star-PAP complex...

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Section: Resultsmentioning

confidence: 94%

CKIα Is Associated with and Phosphorylates Star-PAP and Is Also Required for Expression of Select Star-PAP Target Messenger RNAs

Gonzales

Mellman

Anderson

2008

Journal of Biological Chemistry

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“…Through modifications of its phosphorylation state, IRBIT may act as a sensor of oxidative stress, which is recruited by CPSF to attenuate the polyadenylation state of specific mRNA targets. Alterations of the cellular environment such as oxidative stress lead to induced transcription of cytoprotective genes and consequently to accumulation of the corresponding transcripts and enhanced translation (19). Recent evidence suggests that the cell has evolved specific mechanisms for 3Ј processing of antioxidant response mRNAs (15).…”

Section: Discussionmentioning

confidence: 99%

“…Phosphorylation of IRBIT is crucial for both interaction with Fip1 and regulation of polyadenylation. Furthermore, oxidative stress mediated by tert-butylhydroquinone (tBHQ), a known inducer of antioxidant response genes (19), alters IRBIT phosphorylation state in vivo and in parallel stabilizes the interaction with CPSF and promotes its cytoplasmic redistribution. These findings suggest more versatile functions for IRBIT than expected and raise the possibility that IRBIT modulates the polyadenylation of specific mRNAs in a stimulus-dependent way.…”

mentioning

confidence: 99%

Inositol 1,4,5-Triphosphate Receptor-binding Protein Released with Inositol 1,4,5-Triphosphate (IRBIT) Associates with Components of the mRNA 3′ Processing Machinery in a Phosphorylation-dependent Manner and Inhibits Polyadenylation

Kiefer

Mizutani

Iemura

et al. 2009

Journal of Biological Chemistry

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IRBIT is a recently identified protein that modulates the activities of both inositol 1,4,5-triphosphate receptor and pancreas-type Na ؉ /HCO 3 ؊ cotransporter 1, and the multisite phosphorylation of IRBIT is required for achieving this modulatory action. Here, we report the identification of the cleavage and polyadenylation specificity factor (CPSF), which is a multi-protein complex involved in 3 processing of mRNA precursors, as an additional binding partner for IRBIT. We found that IRBIT interacted with CPSF and was recruited to an exogenous polyadenylation signal-containing RNA. The main target for IRBIT in CPSF was Fip1 subunit, and the phosphorylation of the serine-rich region of IRBIT was required both for direct association with Fip1 in vitro and for redistribution of Fip1 into the cytoplasm of intact cells. Furthermore, tert-butylhydroquinone (tBHQ), an agent that induces oxidative stress, increased the phosphorylation level of IRBIT in vivo and in parallel enhanced the interaction between IRBIT and CPSF and promoted the cytoplasmic distribution of endogenous Fip1. In addition to CPSF, IRBIT interacted in vitro with poly(A) polymerase (PAP), which is the enzyme recruited by CPSF to elongate the poly(A) tail, and inhibited PAP activity in a phosphorylation-dependent manner. These findings raise the possibility that IRBIT modulates the polyadenylation state of specific mRNAs, both by controlling the cytoplasmic/nuclear partitioning of Fip1 and by inhibiting PAP activity, in response to a stimulus that alters its phosphorylation state.The inositol 1,4,5-triphosphate (IP 3 ) 3 receptors (IP 3 Rs) are IP 3 -gated Ca 2ϩ channels located on intracellular Ca 2ϩ stores. When the cell is exposed to a stimulus, IP 3 is produced as a second messenger and mediates the release of Ca 2ϩ by interacting with IP 3 Rs. We previously identified an IP 3 R-binding protein termed IRBIT (IP 3 R-binding protein released with inositol 1,4,5-triphosphate) that interacts with the IP 3 -binding core domain of IP 3 R and is dissociated from IP 3 R by physiological concentrations of IP 3 (1). IRBIT binds to IP 3 R through its N-terminal phosphorylated region and suppresses IP 3 R activity at the resting state by blocking IP 3 access to IP 3 R. When cells are exposed to a stimulus resulting in high concentration of IP 3 , IP 3 displaces IRBIT and activates IP 3 R. From these findings, it was speculated that IRBIT regulates Ca 2ϩ release by setting the threshold of IP 3 concentration required for activation of IP 3 R (2). Besides its function in the regulation of IP 3 R activity, IRBIT also binds to and activates pancreas-type Na ϩ /HCO 3 Ϫ cotransporter 1 (pNBC1), indicating a role in the regulation of intracellular and extracellular pH (3). Interestingly, although interactions with IP 3 R and pNBC1 each show unique properties, they also share common features, such the requirement of the N-terminal phosphorylated region (2, 3). The finding that IRBIT binds to and regulates both IP 3 R and pNBC1 suggests that IRBIT is a multifunctional...

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“…28,29) To probe whether geniposide could activate Nrf2, primary hippocampal neurons were treated with geniposide for the indicated times and concentrations and followed by the analysis of expression of nuclear and cytosolic proteins by western blotting. Treatment with geniposide induced the expression of Nrf2 in cytoplasm and accumulation in nucleus.…”

Section: Geniposide Inhibits Sin-1-induced Hippocampal Neuron Deathmentioning

confidence: 99%

Geniposide Induces the Expression of Heme Oxygenase-1 via PI3K/Nrf2-Signaling to Enhance the Antioxidant Capacity in Primary Hippocampal Neurons

Yin

Liu

Zheng

et al. 2010

Biological & Pharmaceutical Bulletin

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Oxidative stress in brain is emerging as a potential causal factor in aging and age-related neurodegenerative disorders. A large body of evidence shows that induction of endogenous antioxidative proteins seems to be a reasonable strategy for delaying the progression of cell injury. In this study, geniposide upregulates the expression of heme oxygenase-1 (HO-1) to attenuate the cell apoptosis induced by 3-morpholinosydnonimine hydrochloride (SIN-1) in primary cultured hippocampal neurons. Furthermore, geniposide induces the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and activation of phosphatidylinositol 3-kinase (PI3K) in the presence of oxidative stress, and both LY294002 (a specific inhibitor of PI3K) and Zinc protoporphyrin (ZnPP, an inhibitor of HO-1) decrease the cytoprotective action of geniposide in hippocampal neurons. Taken together, the novel cytoprotective mechanism of geniposide to antagonize oxidative stress may be involved in PI3K-and Nrf2-mediated upregulation of the antioxidative enzyme HO-1.

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Induction of Heme Oxygenase-1 (HO-1) and NAD[P]H: Quinone Oxidoreductase 1 (NQO1) by a Phenolic Antioxidant, Butylated Hydroxyanisole (BHA) and Its Metabolite, tert-Butylhydroquinone (tBHQ) in Primary-Cultured Human and Rat Hepatocytes

Cited by 83 publications

References 38 publications

CKIα Is Associated with and Phosphorylates Star-PAP and Is Also Required for Expression of Select Star-PAP Target Messenger RNAs

CKIα Is Associated with and Phosphorylates Star-PAP and Is Also Required for Expression of Select Star-PAP Target Messenger RNAs

Inositol 1,4,5-Triphosphate Receptor-binding Protein Released with Inositol 1,4,5-Triphosphate (IRBIT) Associates with Components of the mRNA 3′ Processing Machinery in a Phosphorylation-dependent Manner and Inhibits Polyadenylation

Geniposide Induces the Expression of Heme Oxygenase-1 via PI3K/Nrf2-Signaling to Enhance the Antioxidant Capacity in Primary Hippocampal Neurons

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