Ornithine decarboxylase activity and polyamine synthesis during kidney hypertrophy

Brandt, John; Pierce, Dorothy A.; Fausto, Nelson

doi:10.1016/0304-4165(72)90253-x

Cited by 70 publications

(18 citation statements)

References 23 publications

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“…Plasma corticosterone levels also rose rapidly, reaching a peak 2 hr after cycloheximide administration and then falling toward control levels by 8 hr (Fig. 1 (10,17,18) and since there was a substantial early rise in plasma corticosterone after cycloheximide administration, it seemed possible that the subsequent rise in enzyme activity was due, not to cycloheximide itself, but to corticosterone released in response to the stress caused by administration of the drug. To test this hypothesis, we adrenalectomized rats 16 hr before injecting cycloheximide.…”

Section: Resultsmentioning

confidence: 99%

Nature of the increase in renal ornithine decarboxylase activity after cycloheximide administration in the rat.

Levine¹,

Nicholson²,

Orth³

1975

Proc. Natl. Acad. Sci. U.S.A.

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The present study was designed to determine whether the increase in rat renal ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity after cycloheximide administration was a primary effect on the kidney or was a secondary effect of adrenal or pituitary hormones released in response to the drug. Renal ornithine decarboxylase activity was reduced approximately 70% 1 hr after intraperitoneal administration of doses of cycloheximide that also inhibited renal protein synthesis by 68-95% within 1 hr. Protein synthesis began to recover by the second hour, accompanied by a rise in decarboxylase activity that reached a peak about six times greater than pretreatment values at 8 hr, then gradually declined to preinjection levels by 16 hr. Peak ornitlhine decarboxylase activity was directly proportional to cycloheximide doses up to 250 Mg; larger doses, which almost abolished protein synthesis for 8 hr, were inhibitory. Plasma corticosterone rose rapidly after cycloheximide, reached a peak at 2 hr, then fell to baseline by 8 hr. Corticosterone response was also dose-dependent up to 250 Mg, but larger doses were inhibitory. Adrenalectomy did not reduce decarboxylase activity response to cycloheximide, nor did cortisol administration enhance it. Hypophysectomy greatly reduced baseline renal decarboxylase activity within 9 hr and all but abolished the increase in enzyme activity normally seen after cycloheximide administration to the intact rat. The hypophysectomized animal exhibited apparent increased sensitivity to cyclohieximide, since a smaller dose of the drug caused a reduction in renal protein synthesis similar to that seen with a larger dose in the intact rat. As protein synthesis was recovering in the hypophysectomized animals, renal decarboxylase activity responded adequately to the injection of a crude pituitary extract. These data suggest that renal ornithine decarboxylase turnover is rapid, that baseline activity is maintained by new protein synthesis, and that the increase in renal enzyme activity after cyclolieximide is in large part dependent upon pituitary hormone action.

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Section: Resultsmentioning

confidence: 99%

Nature of the increase in renal ornithine decarboxylase activity after cycloheximide administration in the rat.

Levine¹,

Nicholson²,

Orth³

1975

Proc. Natl. Acad. Sci. U.S.A.

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“…15 Ornithine decarboxylase, the initial enzyme in polyamine synthesis, is induced prior to organ growth and proliferation and is considered to be essential for regeneration. 18,19 Thymidine kinase, the enzyme that phosphorylates thymidine prior to its incorporation into deoxyribonucleic acid, is also induced in proliferating tissue 20,21 and has been used widely as a biochemical index of regeneration. 13 Both ornithine decarboxylase activity at 6 h and hepatic thymidine kinase activity at 48 h after partial hepatectomy were greater in the animals having had a prior partial portal vein ligation procedure than in those without this procedure.…”

Section: Discussionmentioning

confidence: 99%

Effect of Partial Portal Vein Ligation on Hepatic Regeneration

Kahn

Kajani

Zeng

et al. 1988

Journal of Investigative Surgery

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To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p < 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p < 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection. Keywords hepatic regeneration; portal hypertension; cirrhosis; liver growth; protal blood flow The origin and nature of the factors that control hepatic regeneration remain unresolved. Portal blood has been shown to be hepatotrophic as compared to peripheral blood. 1 However, controversy continues to surround the relative importance of the qualitative changes (hormonal factors) and the quantitative changes (blood flow parameters) in portal blood that occur after partial hepatectomy as they relate to the hepatic regeneration that occurs after a partial hepatic resection. 1-8 The pancreatic hormones, insulin and glucagon, have been shown to modulate, at least in part, the regenerative response that occurs after partial hepatectomy. 1-5 These data, however, do not negate an important role for hepatic blood flow, particularly portal venous blood flow, in the regulation of hepatic regeneration following partial hepatectomy. [6][7][8] The role of hepatic blood flow in modulating liver regeneration was first suggested by the observation that hepatic atrophy occurs after an Eck fistula (end-to-side portal caval shunt). 6 This hepatic atrophy was thought to be the result of a reduced hepatic blood flow,

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“…The level of ODC activity in kidneys was approximately 300-fold the hepatic level. Even in presence of this high control level, unilateral nephrectomy was capable of inducing ODC in the regenerating kidney (24). Therefore, the carcinogenicity and possible tumor promoting activity of chloroform in rat kidney would appear not to be associated with the induction of ODC.…”

Section: Discussionmentioning

confidence: 94%

“…The function of this high level of ODC activity in male kidney is unknown; however, after unilateral nephrectomy, a fourfold increase of ODC activity occurred 24 (20). Chloroform (750 mg/kg body weight), which resulted in a 43.5-fold enhancement of rat liver ODC activity (Table 1), caused a 35% reduction of kidney ODC activity (Table 2).…”

Section: Renal Odc Activitymentioning

confidence: 99%

Chloroform induction of ornithine decarboxylase activity in rats.

Savage¹,

Westrich²,

Guion³

et al. 1982

Environ Health Perspect

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Chloroform is a drinking water contaminant that has been demonstrated to be carcinogenic to mice and rats resulting in an increased incidence of liver and kidney tumors, respectively. The mechanism of chloroform carcinogenicity might be by tumor initiation and/or promotion. Since induction of ornithine decarboxylase (ODC) activity has been proposed as a molecular marker for tumor promoters, we have investigated the effect of chloroform on ODC activity in rats. Chloroform induced a dose-dependent increase of hepatic ODC with an apparent threshold at 100 mg/kg body weight. Female rats were two to four times more susceptible to chloroform. Upon daily dosing of chloroform for 7 days the liver became less susceptible, with the last dose of chloroform resulting in only 10o of the activity observed after a single dose. Nuclear RNA polymerase I activity was also induced by chloroform. Chloroform, rather than increasing the activity of renal ODC, resulted in a 35% reduction. The induction by chloroform of hepatic ODC activity might be associated with regenerative hyperplasia while the renal carcinogenicity of chloroform could not be demonstrated to be associated with ODC induction.

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Ornithine decarboxylase activity and polyamine synthesis during kidney hypertrophy

Cited by 70 publications

References 23 publications

Nature of the increase in renal ornithine decarboxylase activity after cycloheximide administration in the rat.

Nature of the increase in renal ornithine decarboxylase activity after cycloheximide administration in the rat.

Effect of Partial Portal Vein Ligation on Hepatic Regeneration

Chloroform induction of ornithine decarboxylase activity in rats.

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