Polyamine biosynthesis in rabbit perfused heart under various degrees of oxygen tension

Casti, A; Corti, Angelo; Orlandini, Giovanni; Drusiani, F; Calderera, C.M.

doi:10.1016/0024-3205(78)90391-0

Cited by 8 publications

(1 citation statement)

References 14 publications

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“…The antizyme-expressing transgenic mice should provide a useful model in which to evaluate the role of enhanced ODC activity and polyamine content in response to various stresses, including aortic and pulmonary artery constriction, hypoxia, exercise, adrenergic agonists and thyroxine, all of which have been shown previously to be associated with increased ODC activity, increased polyamine content and cardiac hypertrophy [47][48][49][50][51][52][53][54][55]. Several previous studies [38,39,52,[56][57][58] have attempted to examine the importance of such induction by using inhibitors of polyamine synthesis such as DFMO, 1,3-diaminopropanol and 1,3-diaminopropane.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline-induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy

Mackintosh

Feith

Shantz

et al. 2000

Biochemical Journal

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Two lines of transgenic mice were produced with constitutive expression of antizyme-1 in the heart, driven from the cardiac alpha-myosin heavy chain promoter. The use of engineered antizyme cDNA in which nucleotide 205 had been deleted eliminated the need for polyamine-mediated frameshifting, normally necessary for translation of antizyme mRNA, and thus ensured the constitutive expression of antizyme. Antizyme-1 is thought to be a major factor in regulating cellular polyamine content, acting both to inhibit ornithine decarboxylase (ODC) activity and to target it for degradation, as well as preventing polyamine uptake. The two transgenic lines had substantial, but different, levels of antizyme in the heart, as detected by Western blotting and by the ability of heart extracts to inhibit exogenous purified ODC. Despite the high levels of antizyme, endogenous ODC activity was not completely abolished, with 10-39% remaining, depending on the transgenic line. Additionally, a relatively small decrease (30-32%) in cardiac spermidine content was observed, with levels of putrescine and spermine unaffected. Interestingly, although the two lines of transgenic mice had different antizyme expression levels, they had almost identical cardiac polyamine content. When treated with a single acute dose of isoprenaline (isoproterenol), cardiac ODC activity and putrescine content were substantially increased (by 14-fold and 4.7-fold respectively) in non-transgenic littermate mice, but these increases were completely prevented in the transgenic mice from both founder lines. Prolonged exposure to isoprenaline also caused increases in cardiac ODC activity and polyamine content, as well as an increase in cardiac growth, in non-transgenic mice. Although the increases in cardiac ODC activity and polyamine content were prevented in the transgenic mice from both founder lines, the increase in cardiac growth was unaffected. These transgenic mice thus provide a valuable model system in which to study the importance of polyamine levels in cardiac growth and electrophysiology in response to stress.

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Section: Discussionmentioning

confidence: 99%

Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline-induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy

Mackintosh

Feith

Shantz

et al. 2000

Biochemical Journal

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Relationship between the in-situ activity of ornithine decarboxylase and contractile function of the rabbit papillary muscle

Boucek¹,

Olson²,

Boerth³

1983

Basic Res Cardiol

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The relationship between isometric contraction and myocardial ornithine decarboxylase (ODC; EC.4.1.1.17) activity was studied in right ventricular papillary muscles isolated from rabbits. ODC specific activity and polyamine content were significantly increased in papillary muscles contracting isometrically 90 times per minute at the apex of the length-tension relationship for 4 to 5 hours when compared with paired non-contracting muscles or isometrically contracting muscles stimulated at 30 times per min. The increase in ODC activity appeared to be due to new protein synthesis since cycloheximide blocked the increase in ODC activity without affecting isometric function. Thus, the present results suggest that increased contractile demands of the heart may stimulate the synthesis of myocardial ODC, increase ODC activity and polyamine content.

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Effect of polyamines on perfused rat heart contractility

Bazzani

Genedani

Bertolini

1985

Pharmacological Research Communications

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The influence of polyamines (putrescine, spermidine and spermine) on heart contractility was studied using perfused rat ventricle strips (2 X 10 mm), electrically driven at 1 Hz. Putrescine (100 microM) caused a negative inotropic effect gradually increasing in intensity, whereas spermidine and spermine (10 and 100 microM) caused a sharp, positive inotropic effect, followed by a rapid and more marked fall. The possibility that these effects of polyamines on heart contractility may be due to their role in Ca++ fluxes and mobilization, and in membrane functions, is discussed.

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Polyamine biosynthesis in rabbit perfused heart under various degrees of oxygen tension

Cited by 8 publications

References 14 publications

Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline-induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy

Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline-induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy

Relationship between the in-situ activity of ornithine decarboxylase and contractile function of the rabbit papillary muscle

Effect of polyamines on perfused rat heart contractility

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