The effects of Eucalyptus terpenes on hepatic cytochrome P450 CYP4A, peroxisomal Acyl CoA oxidase (AOX) and peroxisome proliferator activated receptor alpha (PPARα) in the common brush tail possum (Trichosurus vulpecula)

Ngo, Suong N.T.; Stupans, Ieva

doi:10.1016/s1532-0456(03)00197-2

Cited by 14 publications

(8 citation statements)

References 31 publications

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“…Recent studies document involvement of CYPs in detoxification processes in koalas ( Phascolarctos cinereus ) and in several species of woodrats ( Neotoma lepida ) (Haley et al , 2007b; Haley et al , 2007a; Skopec et al , 2007; El-Merhibi et al , 2008; Haley et al , 2008; Magnanou et al , 2009). Furthermore, members of the 3A subfamily of CYPs were recently characterized from koala and the Eastern gray kangaroo ( Macropus giganteus ) (El-Merhibi et al , 2011; El-Merhibi et al , 2012) and the 4A subfamily in the koala and common bush tail possum ( Trichosurus vulpecula) (Ngo et al , 2003; Ngo et al , 2006). …”

Section: Introductionmentioning

confidence: 99%

Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

Wilderman

Jang

Malenke

et al. 2014

Toxicology and Applied Pharmacology

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Mammalian detoxification processes have been the focus of intense research, but little is known about how wild herbivores process plant secondary compounds, many of which have medicinal value or are drugs. cDNA sequences that code for three enzymes of the cytochrome P450 (CYP) 2B subfamily, here termed 2B35, 2B36, and 2B37 have been recently identified from a wild rodent, the desert woodrat (Malenke et al., 2012). Two variant clones of each enzyme were engineered to increase protein solubility and to facilitate purification, as reported for CYP2B enzymes from multiple species. When expressed in E. coli each of the woodrat proteins gave the characteristic maximum at 450 nm in a reduced carbon monoxide difference spectrum but generally expressed at lower levels than rat CYP2B1. Two enzymes, 2B36 and 2B37, showed dealkylation activity with the model substrates 7-ethoxy-4-(trifluoromethyl)coumarin and 7-benzyloxyresorufin, whereas 2B35 was inactive. Binding of the monoterpene (+)-α-pinene produced a Type I shift in the absorbance spectrum of each enzyme. Mutation of 2B37 at residues 114, 262, or 480, key residues governing ligand interactions with other CYP2B enzymes, did not significantly change expression levels or produce the expected functional changes. In summary, two catalytic and one ligand-binding assay are sufficient to distinguish among CYP2B35, 2B36, and 2B37. Differences in functional profiles between 2B36 and 2B37 are partially explained by changes in substrate recognition site residue 114, but not 480. The results advance our understanding of the mechanisms of detoxification in wild mammalian herbivores and highlight the complexity of this system.

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Section: Introductionmentioning

confidence: 99%

Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

Wilderman

Jang

Malenke

et al. 2014

Toxicology and Applied Pharmacology

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“…2000, 2006; Pass & McLean 2002; Pass et al. 2002; Ngo et al 2003; Sorensen et al. 2007) and that herbivores consuming large quantities of PSCs have higher activities of some biotransformation enzymes (Ngo et al.…”

Section: The Imi Hypothesismentioning

confidence: 99%

Nutritional toxicology of mammals: regulated intake of plant secondary compounds

Torregrossa

Dearing²

2009

Functional Ecology

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Summary 1.Many mammalian herbivores continually face the possibility of being poisoned by the natural toxins in the plants they consume. A recent key discovery in this area is that mammalian herbivores are capable of regulating the dose of plant secondary compounds (PSCs) ingested. 2. The 'regulation model' describes the factors driving ingestion of PSCs by mammals and can be dissected into two separate hypotheses related to meal size and inter-meal interval (IMI). Testing these hypotheses independently yields a more thorough understanding of the underlying and potentially interconnected mechanisms. 3. Three mechanisms could influence the size of meals that contain PSCs. These are the plasma concentration of PSCs, conditioned learning, and activation of bitter receptors in the intestine. 4. Two mechanisms are proposed to govern the IMI. The first predicts that IMI is dependent on the concentration of PSC metabolites in the plasma; feeding will not resume until metabolite concentrations are acceptable for further ingestion of PSCs. The second hypothesis proposes that the intestinal bitter receptors modulate IMI through release of satiety compounds.

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“…It is thought that specialists have evolved biotransformation pathways and capacities specific to the chemistry of a single plant species (Freeland and Janzen 1974). Recent studies using pharmacological approaches support this idea (Ngo et al 2003(Ngo et al , 2006Haley et al 2007a, b).…”

Section: Introductionmentioning

confidence: 99%

“…Specialists are assumed to have evolved the capacity to biotransform the PSCs of their preferred plant species (Freeland and Janzen 1974;Ngo et al 2003;Shipley et al 2006;Ngo et al 2006;Haley et al 2007a, b), and therefore may not require behavioral regulation at PSC concentrations below the doses typically ingested. Specialists consuming novel PSCs, i.e., unlike those found in their preferred plant species, should not have a detoxification advantage and, thus, are expected to behaviorally regulate to the same extent or to a greater extent as generalists.…”

Section: Introductionmentioning

confidence: 99%

Testing the diet-breadth trade-off hypothesis: differential regulation of novel plant secondary compounds by a specialist and a generalist herbivore

2011

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Specialist herbivores are predicted to have evolved biotransformation pathways that can process large doses of secondary compounds from the plant species on which they specialize. It is hypothesized that this physiological specialization results in a trade-off such that specialists may be limited in ability to ingest novel plant secondary compounds (PSCs). In contrast, the generalist foraging strategy requires that herbivores alternate consumption of plant species and PSC types to reduce the possibility of over-ingestion of any particular PSC. The ability to behaviorally regulate is a key component of this strategy. These ideas underpin the prediction that in the face of novel PSCs, generalists should be better able to maintain body mass and avoid toxic consequences compared to specialists. We explored these predictions by comparing the feeding behavior of two herbivorous rodents: a juniper specialist, Neotoma stephensi, and a generalist, Neotoma albigula, fed diets with increasing concentrations of phenolic resin extracted from the creosote bush (Larrea tridentata), which produces a suite of PSCs novel to both species. The specialist lost more mass than the generalist during the 15-day trial. In addition, although the specialist and generalist both regulated phenolic resin intake by reducing meal size while on the highest resin concentration (4%), the generalist began to regulate intake on the 2% diet. The ability of the generalist to regulate intake at a lower PSC concentration may be the source of the generalist's performance advantage over the specialist. These data provide evidence for the hypothesis that the specialist's foraging strategy may result in behavioral as well as physiological trade-offs in the ability to consume novel PSCs.

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The effects of Eucalyptus terpenes on hepatic cytochrome P450 CYP4A, peroxisomal Acyl CoA oxidase (AOX) and peroxisome proliferator activated receptor alpha (PPARα) in the common brush tail possum (Trichosurus vulpecula)

Cited by 14 publications

References 31 publications

Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

Nutritional toxicology of mammals: regulated intake of plant secondary compounds

Testing the diet-breadth trade-off hypothesis: differential regulation of novel plant secondary compounds by a specialist and a generalist herbivore

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