Involvement of Endoplasmic Reticulum Stress in Hereditary Tyrosinemia Type I

Bergeron, Anne; Jorquera, Rossana; Orejuela, Diana; Tanguay, Robert M.

doi:10.1074/jbc.m506804200

Cited by 33 publications

(27 citation statements)

References 49 publications

(50 reference statements)

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“…Studies on human HT1 and its animal models have shown that the accumulation of MAA, FAA, succinylacetoacetate, and succinylacetone causes direct tissue damage (Lindblad et al, 1977;Grompe et al, 1993;Sun et al, 2000;Aponte et al, 2001;Jorquera and Tanguay, 2001;Bergeron et al, 2006). In this study, we found that treatment of Arabidopsis wild-type seedlings with succinylacetone is able to mimic the sscd1 cell death phenotype (Fig.…”

Section: Discussionsupporting

confidence: 48%

Disruption of Fumarylacetoacetate Hydrolase Causes Spontaneous Cell Death under Short-Day Conditions in Arabidopsis

et al. 2013

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Fumarylacetoacetate hydrolase (FAH) hydrolyzes fumarylacetoacetate to fumarate and acetoacetate, the final step in the tyrosine (Tyr) degradation pathway that is essential to animals. Deficiency of FAH in animals results in an inborn lethal disorder. However, the role for the Tyr degradation pathway in plants remains to be elucidated. In this study, we isolated an Arabidopsis (Arabidopsis thaliana) short-day sensitive cell death1 (sscd1) mutant that displays a spontaneous cell death phenotype under short-day conditions. The SSCD1 gene was cloned via a map-based cloning approach and found to encode an Arabidopsis putative FAH. The spontaneous cell death phenotype of the sscd1 mutant was completely eliminated by further knockout of the gene encoding the putative homogentisate dioxygenase, which catalyzes homogentisate into maleylacetoacetate (the antepenultimate step) in the Tyr degradation pathway. Furthermore, treatment of Arabidopsis wild-type seedlings with succinylacetone, an abnormal metabolite caused by loss of FAH in the Tyr degradation pathway, mimicked the sscd1 cell death phenotype. These results demonstrate that disruption of FAH leads to cell death in Arabidopsis and suggest that the Tyr degradation pathway is essential for plant survival under short-day conditions.

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Section: Discussionsupporting

confidence: 48%

Disruption of Fumarylacetoacetate Hydrolase Causes Spontaneous Cell Death under Short-Day Conditions in Arabidopsis

et al. 2013

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“…For example, treatment of cells in culture with purified FAA is able to cause a number of toxic effects including DNA mutagenesis, ER stress, oxidative stress, mitochondrial dysfunction, and activation of apoptosis (15)(16)(17)(18)20). Additionally, animals mutant for both HPD and FAH that are given homogentisate demonstrate the rapid development of liver and kidney damage (14,50).…”

Section: Conservation Of the Tyrosine Degradation Pathway In Worms-mentioning

confidence: 99%

“…Organ damage is likely due to the accumulation of MAA, FAA, and their conversion to succinylacetoacetate (SAA) and succinylacetone (SA) (12). These compounds are highly reactive electrophiles, which can damage proteins and DNA leading to the activation of several stress response pathways as well as apoptotic pathways (13)(14)(15)(16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

The Caenorhabditis elegans K10C2.4 Gene Encodes a Member of the Fumarylacetoacetate Hydrolase Family

Fisher

Page

Lithgow

et al. 2008

Journal of Biological Chemistry

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In eukaryotes and many bacteria, tyrosine is degraded to produce energy via a five-step tyrosine degradation pathway. Mutations affecting the tyrosine degradation pathway are also of medical importance as mutations affecting enzymes in the pathway are responsible for type I, type II, and type III tyrosinemia. The most severe of these is type I tyrosinemia, which is caused by mutations affecting the last enzyme in the pathway, fumarylacetoacetate hydrolase (FAH). So far, tyrosine degradation in the nematode Caenorhabditis elegans has not been studied; however, genes predicted to encode enzymes in this pathway have been identified in several microarray, proteomic, and RNA interference (RNAi) screens as perhaps being involved in aging and the control of protein folding. We sought to identify and characterize the genes in the worm tyrosine degradation pathway as an initial step in understanding these findings. Here we describe the characterization of the K10C2.4, which encodes a homolog of FAH. RNAi directed against K10C2.4 produces a lethal phenotype consisting of death in young adulthood, extensive damage to the intestine, impaired fertility, and activation of oxidative stress and endoplasmic stress response pathways. This phenotype is due to alterations in tyrosine metabolism as increases in dietary tyrosine enhance it, and inhibition of upstream enzymes in tyrosine degradation with RNAi or genetic mutations reduces the phenotype. We also use our model to identify genes that suppress the damage produced by K10C2.4 RNAi in a pilot genetic screen. Our results establish worms as a model for the study of type I tyrosinemia.

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“…Clinical study revealed that targeted therapy against TNF-α could downregulate epithelial cell apoptosis and promotes barrier repair in active Crohn's disease [26]. Mutant mouse with TNF-α overexpression may cause IEC FFA (fumarylacetoacetate) accumulation [27], which has been proven as a potent inducer of ER stress [28]. Since whether TNF-α alone could induce ER stress and apoptosis is controversial in vitro [29], and previous studies revealed that IFN-γ prime the response of Caco-2 cells to TNF-α through induction of TNFR2 expression [15] or potentiating TNF-related apoptosis-inducing ligand [30], a combination of IFN-γ and TNF-α was used.…”

Section: Discussionmentioning

confidence: 99%

Berberine Ameliorates Pro-inflammatory Cytokine-Induced Endoplasmic Reticulum Stress in Human Intestinal Epithelial Cells In Vitro

et al. 2011

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Endoplasmic reticulum stress (ER stress) in intestinal epithelial cells (IECs) plays an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). The aim of this study is to explore the potential of berberine (BBR) in regulating pro-inflammatory cytokine-induced ER stress and apoptosis in IECs. ER stress in cultured Caco-2 cells was induced by IFN-γ/TNF-α and tunicamycin, respectively. The experimental groups were pretreated with BBR. Cell viability was determined by MTT assay. In vitro apoptosis was examined by flow cytometry using annexin V-FITC labeling. The molecular markers of ER stress, including GRP-78, p-JNK, caspase-12, and cleaved caspase-3 were analyzed by Western blot. Xbp-1 mRNA splicing was detected by RT-PCR. Pretreatment of BBR helped to survive in cytokine-induced Caco-2 cells. BBR significantly attenuated cytokine-induced Caco-2 apoptosis. GRP78 expression and xbp-1 mRNA splicing were enhanced significantly in the presence of IFN-γ/TNF-α and tunicamycin, and they could be dampened by BBR. Further study revealed BBR could downregulate JNK phosphorylation, and the level of caspase-12 and cleaved caspase-3. Berberine can ameliorate pro-inflammatory cytokines induced ER stress in vitro, and it might be one of the targeted therapeutic agents for IBD.

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Involvement of Endoplasmic Reticulum Stress in Hereditary Tyrosinemia Type I

Cited by 33 publications

References 49 publications

Disruption of Fumarylacetoacetate Hydrolase Causes Spontaneous Cell Death under Short-Day Conditions in Arabidopsis

Disruption of Fumarylacetoacetate Hydrolase Causes Spontaneous Cell Death under Short-Day Conditions in Arabidopsis

The Caenorhabditis elegans K10C2.4 Gene Encodes a Member of the Fumarylacetoacetate Hydrolase Family

Berberine Ameliorates Pro-inflammatory Cytokine-Induced Endoplasmic Reticulum Stress in Human Intestinal Epithelial Cells In Vitro

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