Biochemistry of the Peroxisome in the Liver Cell

Sies, Helmut

doi:10.1002/anie.197407061

Cited by 61 publications

(13 citation statements)

References 155 publications

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“…The colocalization of catalase with H 2 O 2 -producing oxidases in peroxisomes attracted the attention of early investigators to the important role of this organelle in the metabolism of ROS (De Duve and Baudhuin 1966;Oshino et al 1973;Sies 1974). The enzymes in mammalian peroxisomes producing H 2 O 2 and O 2 · , as well as the recently discovered inducible NO synthase generating nitric oxide are compiled in Table 2.…”

Section: Enzymes In Peroxisomes That Produce Rosmentioning

confidence: 98%

Mammalian peroxisomes and reactive oxygen species

Schrader

Fahimi

2004

Histochem Cell Biol

156

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The central role of peroxisomes in the generation and scavenging of hydrogen peroxide has been well known ever since their discovery almost four decades ago. Recent studies have revealed their involvement in metabolism of oxygen free radicals and nitric oxide that have important functions in intra- and intercellular signaling. The analysis of the role of mammalian peroxisomes in a variety of physiological and pathological processes involving reactive oxygen species (ROS) is the subject of this review. The general characteristics of peroxisomes and their enzymes involved in the metabolism of ROS are briefly reviewed. An expansion of the peroxisomal compartment with proliferation of tubular peroxisomes is observed in cells exposed to UV irradiation and various oxidants and is apparently accompanied by upregulation of PEX genes. Significant reduction of peroxisomes and their enzymes is observed in inflammatory processes including infections, ischemia-reperfusion injury, and allograft rejection and seems to be related to the suppressive effect of tumor necrosis factor-alpha on peroxisome function and peroxisome proliferator activated receptor-alpha. Xenobiotic-induced proliferation of peroxisomes in rodents is accompanied by the formation of hepatic tumors, and evidently the imbalance in generation and decomposition of ROS plays an important role in this process. In PEX5-/- knockout mice lacking functional peroxisomes severe alterations of mitochondria in various organs are observed which seem to be due to a generalized increase in oxidative stress confirming the important role of peroxisomes in homeostasis of ROS and the implications of its disturbances for cell pathology.

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Section: Enzymes In Peroxisomes That Produce Rosmentioning

confidence: 98%

Mammalian peroxisomes and reactive oxygen species

Schrader

Fahimi

2004

Histochem Cell Biol

156

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“…The Habilitation thesis was written in 1971, entitled Das Peroxysom im Hepatozyten, and a review article appeared in 1974 [10]. Leopold FlohØ, then at Tübingen, being one of the early students in the newly established curriculum of biochemistry, was working on the enzymology of glutathione peroxidase, an enzyme yet to be fully appreciated.…”

Section: Research Group At Munich: Glutathione and Hydroperoxide Metamentioning

confidence: 99%

Biological Redox Systems and Oxidative Stress

Sies

2007

Cell. Mol. Life Sci.

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This account revolves around fascination and excitement with science. Early curiosity and fortunate opportunities can lead to a satisfying career. The privilege of performing basic research in biochemistry and molecular biology at a university coupled with teaching motivated students and working with dedicated co-workers makes for sustained thrust in the advance of knowledge. Research fields centered around cellular redox systems, oxidants and antioxidants, and the concept of oxidative stress. A noteworthy aspect is the global network of scientists joining in these endeavors worldwide.

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“…However, the inhibitory effect of apocynin was restored following treatment with H 2 O 2 and horseradish peroxidase (33). Hepatocytes are known to contain high activities of peroxidases (61,62) and to exhibit endogenous H 2 O 2 formation (61,63), which are prerequisites for the inhibitory action of apocynin on NADPH oxidases. This may explain why in rat hepatocytes after a 30-min preincubation with apocynin, CD95L-induced ROS formation via NADPH oxidase is inhibited.…”

Section: Cd95l-induced Early Oxidative Stressmentioning

confidence: 99%

Involvement of NADPH Oxidase Isoforms and Src Family Kinases in CD95-dependent Hepatocyte Apoptosis

Reinehr

Becker

Eberle

et al. 2005

Journal of Biological Chemistry

224

204

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CD95 ligand (CD95L) triggers a rapid formation of reactive oxygen species (ROS) as an upstream event of CD95 activation and apoptosis induction in rat hepatocytes. This ROS response was sensitive to inhibition by diphenyleneiodonium, apocynin, and neopterin, suggestive of an involvement of NADPH oxidases. In line with this, hepatocytes expressed mRNAs not only of the phagocyte gp91 phox (Nox 2), but also of the homologs Nox 1 and 4 and Duox 1 and 2, as well as the regulatory subunit p47 phox . gp91 phox (Nox 2) and p47 phox were also identified at the protein level in rat hepatocytes. CD95L induced within 1 min ceramide formation and serine phosphorylation of p47 phox , which was sensitive to inhibitors of sphingomyelinase and protein kinase C (PKC). These inhibitors and p47 phox protein knockdown inhibited the early CD95L-induced ROS response, suggesting that ceramide and PKC are upstream events of the CD95L-induced Nox/Duox activation. CD95L also induced rapid activation of the Src family kinase Yes, being followed by activation of c-Src, Fyn, and c-Jun-N-terminal kinases (JNK). Only Yes and JNK activation were sensitive to N-acetylcysteine, inhibitors of NADPH oxidase, PKC, or sphingomyelinase, indicating that the CD95L-induced ROS response is upstream of Yes and JNK but not of Fyn and c-Src activation. Activated Yes rapidly associated with the epidermal growth factor receptor (EGFR), which became phosphorylated at Tyr 845 and Tyr 1173 but not at Tyr 1045 . Activated EGFR then triggered an AG1478-sensitive CD95-tyrosine phosphorylation, which was a signal for membrane targeting of the EGFR/CD95 complex, subsequent recruitment of Fasassociated death domain and caspase 8, and apoptosis induction. All of these events were significantly blunted by inhibitors of sphingomyelinase, PKC, NADPH oxidases, Yes, or EGFR-tyrosine kinase activity and after protein knockdown of either p47 phox , Yes, or EGFR. The data suggest that CD95L-induced apoptosis involves a sphingomyelinase-and PKC-dependent activation of NADPH oxidase isoforms, which is required for Yes/EGFR/CD95 interactions as upstream events of CD95 activation.

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Biochemistry of the Peroxisome in the Liver Cell

Cited by 61 publications

References 155 publications

Mammalian peroxisomes and reactive oxygen species

Mammalian peroxisomes and reactive oxygen species

Biological Redox Systems and Oxidative Stress

Involvement of NADPH Oxidase Isoforms and Src Family Kinases in CD95-dependent Hepatocyte Apoptosis

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