Malondialdehyde production from spermine by homogenates of normal and transformed cells

Quash, G.; Ripoll, Huguette; Gazzolo, Louis; Doutheau, Alain; Saba, Adama; Goré, J.

doi:10.1016/0300-9084(87)90241-0

Cited by 17 publications

(7 citation statements)

References 25 publications

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“…Such aldehyde metabolites could in principle directly inhibit the expression of iNOS or, alternatively, may be further metabolized to yield the active inhibitor. Potential aldehyde metabolites of spermine which may contribute to the inhibition of iNOS induction seen with spermine include spermine dialdehyde (SDA) or malon dialdehyde (MDA) which are generated from spermine by polyamine oxidases (Labib & Tomasi, 1981;Quash et al, 1987;Lau et al, 1990). MDA was ineffective in inhibiting nitrite production in LPS-activated macrophages, even when FCS was present, whereas SDA caused a significant inhibition of nitrite accumulation even in the absence of serum (Figure 9).…”

Section: Discussionmentioning

confidence: 99%

The mechanism of the inhibitory effect of polyamines on the induction of nitric oxide synthase: role of aldehyde metabolites

Szabó

Southan

Thiemermann

et al. 1994

British J Pharmacology

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1 We have recently found that in the presence, but not in the absence, of foetal calf serum, spermine inhibits the production of nitric oxide (NO) in cultured J774.2 macrophages stimulated with bacterial endotoxin (lipopolysaccharide; LPS) or with '-interferon (IFN), showing that polyamines may act as suppressants of NO-mediated immune functions. Here, we have studied the mechanisms and the specificity of this inhibitory action. 2 Other polyamines, as well as spermine, inhibit the formation of NO in cultured J774.2 macrophages, with the order of potency being spermine > spermidine >> putrescine = cadaverine. This inhibition of NO formation is not due to any cytotoxic effect of these agents for they neither reduced mitochondrial respiration nor increased the release of lactate dehydrogenase into the supernatant. 3 Spermine is not a direct inhibitor of the activity of iNOS in induced J774.2 cells as measured by its lack of effect on the conversion of L-arginine to L-citrulline in homogenates. Neither spermine, nor its metabolites, interfere with the production of nitrite from NO or act as scavengers of NO. Thus, spermine is an inhibitor of the induction of iNOS. 4 Spermine inhibits nitrite formation in the presence of foetal, newborn or adult bovine serum, but not rat or human serum. 5 The effect of sper mine on nitrite production can be prevented by isoniazid, hydrazine or hydroxylamine, inhibitors of spermine oxidase, as well as by phenylhydrazine, an aldehyde inhibitor. We have, therefore, tested the effects of spermine dialdehyde or malon dialdehyde on the induction of iNOS. Spermine dialdehyde (SDA, 10-M) inhibits nitrite formation by IFN-activated J774.2 cells in the absence of serum when given as a pretreatment but not when given 6 h after stimulation. In contrast, malon dialdehyde was ineffective. Thus, aldehyde metabolites of spermine, such as SDA, account for the inhibitory effect of polyamines on the induction of NOS in vitro. 6 The inhibitory effect of polyamines on iNOS induction appears to be fairly specific to iNOS, for spermine does not inhibit LPS-induced production of prostaglandin F2g or tumour necrosis factor.

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Section: Discussionmentioning

confidence: 99%

The mechanism of the inhibitory effect of polyamines on the induction of nitric oxide synthase: role of aldehyde metabolites

Szabó

Southan

Thiemermann

et al. 1994

British J Pharmacology

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“…Administration of N-2-MPG markedly reduces 3-aminopropanal-modified protein levels and confers significant cerebroprotection in vivo, even when the drug is administered after the onset of brain ischemia in experimental animals subjected to MCAO. For instance, it is possible that N-2-MPG may neutralize the cytotoxicity of other aldehydes in addition to 3-aminopropanal (27)(28)(29)(30). N-2-MPG may also confer some neuroprotective effects by scavenging free radicals and replenishing glutathione supplies (31,32).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal

Ivanova

Batliwalla

Mocco

et al. 2002

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

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Cerebral ischemia stimulates increased activity of polyamine oxidase, a ubiquitous enzyme that catabolizes polyamines to produce 3-aminopropanal. 3-Aminopropanal is a reactive aldehyde that mediates progressive neuronal necrosis and glial apoptosis. Here we report that increased levels of 3-aminopropanal-modified protein levels in humans after aneurysmal subarachnoid hemorrhage correlate with the degree of cerebral injury as measured by admission Hunt͞Hess grade. In vitro screening of clinically approved drugs reveals that N-2-mercaptopropionyl glycine (N-2-MPG), an agent clinically approved for prevention of renal stones in patients with cysteinuria, significantly inhibits the cytotoxicity of 3-aminopropanal. N-2-MPG reacts with 3-aminopropanal to yield a nontoxic thioacetal adduct, as confirmed by electrospray ionization mass spectroscopy. Administration of N-2-MPG in clinically relevant doses to rats significantly reduces cerebral 3-aminopropanal-modified protein immunoreactivity and infarct volume in a standardized model of middle cerebral artery occlusion, even when the agent is administered after the onset of ischemia. These results implicate 3-aminopropanal as a therapeutic target for cerebral ischemia.

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“…The MDA standard was prepared with 1,1,3,1 tetramethoxypropan (Sigma) [16]. All milk samples for enzymatic analysis had been dissolved (1:10) in bidistilled water.…”

Section: Methodsmentioning

confidence: 99%

Polyamine Oxidase and Diamine Oxidase Activities in Acute Ureteral Obstruction

Pavlović¹,

Bjelaković²,

Mitić-Zlatković³

et al. 1998

Nephron

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Objective Human milk (HM) is the ideal food for all newborns and infants. Apart from various bioactive compounds, including cytokines, antibodies, hormones, vitamines, it also contains polyamines, such as spermine (Sp), spermidine (Spd) and putrescine (Put). Aim The present study investigated polyamine metabolism in colostrum and mature human milk by measuring the polyamine oxidase (PAO) and diamine oxidase (DAO) enzyme activities, which are necessary for polyamine catabolism, as well as by determining the malondialdehyde (MDA) levels, the final product of polyamine biodegradation. Methods The PAO, DAO activity and MDA levels were quantified in colostrum (1st and 2nd day) as well as in mature human milk, 30th day of lactation. Findings We found the steady increase of PAO activity and steady decrease of DAO activity and MDA levels during first month of lactation. Conclusion Since the products of PAO activity such as, amino aldehydes and hydrogen peroxide (H 2 O 2 ) might have potential antimicrobial effects, promoting the oxidative stress, it is likely that human milk PAO throughout the lactation period, contributes to the protective effects of human milk.

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Malondialdehyde production from spermine by homogenates of normal and transformed cells

Cited by 17 publications

References 25 publications

The mechanism of the inhibitory effect of polyamines on the induction of nitric oxide synthase: role of aldehyde metabolites

The mechanism of the inhibitory effect of polyamines on the induction of nitric oxide synthase: role of aldehyde metabolites

Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal

Polyamine Oxidase and Diamine Oxidase Activities in Acute Ureteral Obstruction

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