Involvement of polyamines in apoptosis of cardiac myoblasts in a model of simulated ischemia

Tantini, Benedetta; Fiumana, Emanuela; Cetrullo, Silvia; Pignatti, Carla; Bonavita, Francesca; Shantz, Lisa M.; Giordano, Emanuele; Muscari, Claudio; Flamigni, Flavio; Guarnieri, Carlo; Stefanelli, Claudio; Caldarera, Claudio Marcello

doi:10.1016/j.yjmcc.2006.03.002

Cited by 60 publications

(46 citation statements)

References 44 publications

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“…Our observations that Mst did not affect apoptosis in H9c2 cultures are compatible with what we reported in skeletal myoblast cultures (Taylor et al 2001). H9c2 cells do respond to cardiacrelevant apoptotic stimuli, such as hypoxia combined with serum deprivation (Tantini et al 2006). In addition, it is notable that in Mst transgenic mice in which Mst expression was driven by MCK-3E reporter, which restricted the Mst transgene expression to the skeletal muscle, the cardiac mass did not differ from that in WT controls.…”

Section: Discussionsupporting

confidence: 90%

Alterations in myostatin expression are associated with changes in cardiac left ventricular mass but not ejection fraction in the mouse

Artaza

Reisz‐Porszasz

Dow

et al. 2007

Journal of Endocrinology

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Myostatin (Mst) is a negative regulator of skeletal muscle in humans and animals. It is moderately expressed in the heart of sheep and cattle, increasing considerably after infarction. Genetic blockade of Mst expression increases cardiomyocyte growth. We determined whether Mst overexpression in the heart of transgenic mice reduces left ventricular size and function, and inhibits in vitro cardiomyocyte proliferation. Young transgenic mice overexpressing Mst in the heart (Mst transgenic mice (TG) under a muscle creatine kinase (MCK) promoter active in cardiac and skeletal muscle, and Mst knockout (Mst (K/K)) mice were used. Xiscan angiography revealed that the left ventricular ejection fraction did not differ between the Mst TG and the Mst (K/K) mice, when compared with their respective wild-type strains, despite the decrease in whole heart and left ventricular size in Mst TG mice, and their increase in Mst (K/K) animals. The expected changes in cardiac Mst were measured by RT-PCR and western blot. Mst and its receptor (ActRIIb) were detected by RT-PCR in rat H9c2 cardiomyocytes. Transfection of H9c2 with plasmids expressing Mst under muscle-specific creatine kinase promoter, or cytomegalovirus promoter, enhanced p21 and reduced cdk2 expression, when assessed by western blot. A decrease in cell number occurred by incubation with recombinant Mst (formazan assay), without affecting apoptosis or cardiomyocyte size. Anti-Mst antibody increased cardiomyocyte replication, whereas transfection with the Mst-expressing plasmids inhibited it. In conclusion, Mst does not affect cardiac systolic function in mice overexpressing or lacking the active protein, but it reduces cardiac mass and cardiomyocyte proliferation.

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Section: Discussionsupporting

confidence: 90%

Alterations in myostatin expression are associated with changes in cardiac left ventricular mass but not ejection fraction in the mouse

Artaza

Reisz‐Porszasz

Dow

et al. 2007

Journal of Endocrinology

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“…Conversely, the inverse association with spermidine/spermine ratio may represent either an overload of the non-inducible spermine synthase or an increased catabolism of spermine through N-acetylspermine. The role of polyamines in human diseases has recently been claimed in several studies, showing that their production was increased in models of experimentally induced cardiac hypertrophy (23) and that spermidine had detrimental effects on cardiomyocytes under hypoxic stress (24). Accordingly, polyamines were also found increased in patients with heart failure (25).…”

Section: Discussionmentioning

confidence: 96%

Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome

Dalmazi

Quinkler²,

Deutschbein

et al. 2017

European Journal of Endocrinology

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OBJECTIVE: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. DESIGN: Cross-sectional study. METHODS: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. RESULTS: Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabetic patients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases. CONCLUSIONS: Metabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete -oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism. AbstractObjective: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. Design: Cross-sectional study. Methods: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. Results: Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branchedchain and aromatic amino acids, but hi...

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“…The same authors further dissected the anti-apoptotic pathway mediated by DFMO treatment in a subsequent study [57], demonstrating that polyamine depletion through the DFMOmediated ODC inhibition increased p53 but not its phosphorylation, thus highlighting the protective effect of polyamine depletion against DNA damaging agents. A pro-apoptotic role of polyamines has also been demonstrated in cardiomyoblasts in an in vitro model of simulated ischemia able to induce apoptosis [58]. Recent data show activation of JNK, iNOS induction and apoptosis in human cultured SMCs exposed to spermine [59].…”

Section: Polyamines and Apoptosismentioning

confidence: 90%

The Polyamine Pathway as a Potential Target for Vascular Diseases: Focus on Restenosis

Forte¹,

Hellstrand²,

Nilsson³

et al. 2011

CVP

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Involvement of polyamines in apoptosis of cardiac myoblasts in a model of simulated ischemia

Cited by 60 publications

References 44 publications

Alterations in myostatin expression are associated with changes in cardiac left ventricular mass but not ejection fraction in the mouse

Alterations in myostatin expression are associated with changes in cardiac left ventricular mass but not ejection fraction in the mouse

Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome

The Polyamine Pathway as a Potential Target for Vascular Diseases: Focus on Restenosis

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