Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids.

Rinehart, Clifford A.; Canellakis, E.S.

doi:10.1073/pnas.82.13.4365

Cited by 40 publications

(14 citation statements)

References 23 publications

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“…In contrast, studies with several cell lines [40,41] have demonstrated that loading cells with System A amino acids, including the nonmetabolisable alpha‐amino‐isobutyrate [41], mimics the action of insulin and other growth factors [40,41]. Such potentially anabolic effects only occur at very high intracellular amino acid concentrations [40,41] but such concentrations are attained in a few hours in L6‐G8C5 cells exposed to high extracellular concentrations of MeAIB (Fig. 10).…”

Section: Discussionmentioning

confidence: 99%

Impaired system A amino acid transport mimics the catabolic effects of acid in L6 cells

Bevington

Brown

Butler

et al. 2002

Eur J Clin Investigation

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Section: Discussionmentioning

confidence: 99%

Impaired system A amino acid transport mimics the catabolic effects of acid in L6 cells

Bevington

Brown

Butler

et al. 2002

Eur J Clin Investigation

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“…Basal levels of ODC are low, but enzyme activity increases rapidly in response to a variety of stimuli, including growth factors, insulin, stress, and certain amino acids (Wang and Johnson 1991, Rinehart and Canellakis 1985). ODC has one of the shortest half-lives of any mammalian enzyme and is feedback regulated by polyamines which induce the synthesis of an inhibitor called antizyme (Heller et al, 1976).…”

Section: Polyaminesmentioning

confidence: 99%

“…Although ASN was the most effective, other amino acids transported by one of the Na + -dependent systems could also induce ODC activity (Rinehart et al 1985). Of particular interest was the finding that, in a variety of cell types, the induction of ODC by growth factors and hormones required the presence of ASN, GLN or a similar amino acid (Rinehart and Canellakis, 1985). Neither epidermal growth factor (EGF), nerve growth factor, nor insulin could induce ODC activity unless ASN was present in the medium.…”

Section: Polyaminesmentioning

confidence: 99%

Regulation of intestinal mucosal growth by amino acids

Ray

Johnson

2013

Amino Acids

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Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal mucosal growth, and the inhibition of ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, blocks growth. Certain amino acids, primarily asparagine (ASN) and GLN stimulate ODC activity in a solution of physiological salts. More importantly, their presence is also required before growth factors and hormones such as EGF and insulin are able to increase ODC activity. ODC activity is inhibited by antizyme-1 (AZ) whose synthesis is stimulated by polyamines, thus, providing a negative feedback regulation of the enzyme. In the absence of amino acids mammalian target of rapamycin complex 1 (mTORC1) is inhibited, whereas, mTORC2 is stimulated leading to the inhibition of global protein synthesis but increasing the synthesis of AZ via a cap-independent mechanism. These data, therefore, explain why ASN or GLN is essential for the activation of ODC. Interestingly, in a number of papers, AZ has been shown to inhibit cell proliferation, stimulate apoptosis or increase autophagy. Each of these activities results in decreased cellular growth. AZ binds to and accelerates the degradation of ODC and other proteins shown to regulate proliferation and cell death, such as Aurora-A, Cyclin D1 and Smad1. The correlation between the stimulation of ODC activity and the absence of AZ as influenced by amino acids is high. Not only do amino acids such as ASN and GLN stimulate ODC while inhibiting AZ synthesis, but also amino acids such as lysine, valine and ornithine, which inhibit ODC activity, increase the synthesis of AZ. The question remaining to be answered is whether AZ inhibits growth directly or whether it acts by decreasing the availability of polyamines to the dividing cells. In either case, evidence strongly suggests that the regulation of AZ synthesis is the mechanism through which amino acids influence the growth of intestinal mucosa. This brief article reviews the experiments leading to the information presented above. We also present evidence from the literature that AZ acts directly to inhibit cell proliferation and increase the rate of apoptosis. Finally, we discuss future experiments that will determine the role of AZ in the regulation of intestinal mucosal growth by amino acids.

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“…In the present study, an attempt was made to assess the degree of hormonal stimulation of individual small, non-atretic ovarian follicles by measuring their ornithine decarboxylase activity (L-ornithine carboxy-lyase; EC 4.1.1.17) in relation to follicular size and location within the ovary. This enzyme catalyses the ratelimiting reaction in the biosynthesis of the polyamines, spermidine and spennine (Pegg & Williams-Ashman, 1968) and its activity increases substantially in response to a variety of trophic stimuli including hormones, tumour promoters, nutrient availability and organ regeneration (Schorock, Oakman & Butcher, 1970;Veldhuis & Sweinberg, 1981;Jetten, Ganong, Vandenbark et al 1985;Rinehart & Canellakis, 1985). Its activity is closely related to tissue growth.…”

Section: Introductionmentioning

confidence: 97%

Ornithine decarboxylase activity in small ovarian follicles from the laying hen (Gallus domesticus): a comparison of follicles from several regions of the ovary

Dg¹

1987

Journal of Endocrinology

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Small non-atretic follicles (1.5-250 mg) were collected from four distinct areas of the ovary of the laying hen. These were as follows: the stalks of the two largest preovulatory follicles; the stalks of the third largest preovulatory follicle; the stalks of the fourth and fifth largest preovulatory follicle and zona parenchymatosa. There was an increase in the proportion of small follicles in the size range 1.5-10 mg collected from the stalks of the large yellow yolky preovulatory follicles approaching ovulation, with a corresponding decrease in the number of small follicles in the size group 10-250 mg. In addition, the ornithine decarboxylase activity in follicles collected from regions 1 and 2 was significantly greater than that in small follicles collected from region 4. Since the level of ornithine decarboxylase activity is critically dependent on the degree of hormonal stimulation and growth rate of the tissue, it is suggested, on the basis of the differences in their ornithine decarboxylase activity, that small follicles located on the stalks of the large yolky preovulatory follicles are stimulated by trophic hormones and growth factors to a greater degree than similarly sized follicles located elsewhere in the ovary. It is proposed that this increased stimulation may increase the chances of these small follicles being recruited into the hierarchy.

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Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids.

Cited by 40 publications

References 23 publications

Impaired system A amino acid transport mimics the catabolic effects of acid in L6 cells

Impaired system A amino acid transport mimics the catabolic effects of acid in L6 cells

Regulation of intestinal mucosal growth by amino acids

Ornithine decarboxylase activity in small ovarian follicles from the laying hen (Gallus domesticus): a comparison of follicles from several regions of the ovary

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