Contribution of polyamine oxidase to brain injury after trauma

Doğan, Aclan; Rao, A. Muralikrishna; Başkaya, Mustafa K.; Hatcher, James F.; Temız, Cüneyt; Rao, Venkat K.; Dempsey, Robert J.

doi:10.3171/jns.1999.90.6.1078

Cited by 43 publications

(34 citation statements)

References 21 publications

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“…This simulation also showed that cavitation, if possible, is more likely to be associated with endogenous wave reflections than with the negative phase of the incident blast wave. Tissue cavitation has been proposed as a potential physical mechanism conducive to brain injury (27)(28)(29). The second simulation was intended to evaluate the blast protection properties provided by the ACH.…”

Section: Discussionmentioning

confidence: 99%

In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury

Nyein

Jason²,

Yu³

et al. 2010

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

140

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Section: Discussionmentioning

confidence: 99%

In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury

Nyein

Jason²,

Yu³

et al. 2010

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

140

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“…MDL 72527 treatment resulted in decreased putrescine levels and increased N 1 -acetylspermidine levels after CNS injury Effects of MDL 72527 on putrescine levels after MCAO in SHRs (Dogan et al, 1999b) or TBI in rats (Dogan et al, 1999a) have been reported earlier.…”

Section: Accumulation Of Putrescine Is Maximal At 1 Day After Transiementioning

confidence: 62%

“…Our recent studies in transient focal cerebral ischemia in spontaneously hypertensive rats (SHRs) (Dogan et al, 1999b) and traumatic brain injury (TBI) in SpragueDawley rats (Dogan et al, 1999a) demonstrated that specific inhibition of PAO by N 1 ,N 4 -bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527) attenuated tissue putrescine levels, edema, and ischemic injury volume. The purpose of this study is to show the activation of SSAT by quantifying the accumulated N 1 -acetylspermidine after CNS trauma.…”

mentioning

confidence: 99%

Elevated N¹‐Acetylspermidine Levels in Gerbil and Rat Brains After CNS Injury

Rao

Hatcher

Doğan

et al. 2000

Journal of Neurochemistry

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Abstract:The polyamine system is very sensitive to different pathological states of the brain and is perturbed after CNS injury. The main modifications are significant increases in ornithine decarboxylase activity and an increase in tissue putrescine levels. Previously we have shown that the specific polyamine oxidase (PAO) inhibitor N 1 ,N 4 -bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527) reduced the tissue putrescine levels, edema, and infarct volume after transient focal cerebral ischemia in spontaneously hypertensive rats and traumatic brain injury of Sprague-Dawley rats. In the present study, N 1 -acetylspermidine accumulation was greater in injured brain regions compared with sham or contralateral regions following inhibition of PAO by MDL 72527. This indicates spermidine/spermine-N 1 -acetyltransferase (SSAT) activation after CNS injury. The observed increase in N 1 -acetylspermidine levels at 1 day after CNS trauma paralleled the decrease in putrescine levels after treatment with MDL 72527. This suggests that the increased putrescine formation at 1 day after CNS injury is mediated by the SSAT/PAO pathway, consistent with increased SSAT mRNA after transient ischemia. Key Words: Cerebral ischemia-Spermidine/spermine-N 1 -acetyltransferase -Polyamine oxidase -MDL 72527-Putrescine -Traumatic brain injury-Polyamine interconversion pathway-Polyamines-Ornithine decarboxylase. J. Neurochem. 74, 1106Neurochem. 74, -1111Neurochem. 74, (2000.Putrescine, spermidine, and spermine are endogenous polyamines essential for cellular growth, proliferation, regeneration, and differentiation (Pegg and McCann, 1982;Morgan, 1987;Marton and Pegg, 1995). The metabolism and catabolism of polyamines are highly regulated by the concerted action of six enzymes (Paschen, 1992a,b;Marton and Pegg, 1995). The metabolism of polyamines is regulated by ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase, together with spermidine/spermine synthases, of which ODC is the rate-limiting step for the conversion of ornithine to putrescine. Spermidine/spermine-N 1 -acetyltransferase (SSAT) and polyamine oxidase (PAO) regulate polyamine catabolism and the interconversion of spermine/spermidine back to putrescine (Casero and Pegg, 1993;Woster, 1995). In normal brain tissue it has been estimated that ODC accounts for 30% of putrescine, whereas the remaining 70% is formed through the SSAT/ PAO pathway (Seiler and Bolkenius, 1985;Seiler, 1995).Alterations in polyamine metabolism have been implicated in neuronal degeneration after CNS injury (Paschen, 1992a,b;Schmitz et al

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“…The importance of polyamine oxidases in the mediation of a variety of organ injuries has been documented (8,9,27,35). Previous studies indicate that the induction of SSAT expression in cultured cells is associated with coincidental increases in the expression of ODC and SMO mRNAs (32).…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte-specific ablation of spermine/spermidine-N¹-acetyltransferase gene reduces the severity of CCl₄-induced acute liver injury

Zahedi

Barone

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Activation of spermine/spermidine-N 1 -acetyltransferase (SSAT) leads to DNA damage and growth arrest in mammalian cells, and its ablation reduces the severity of ischemic and endotoxic injuries. Here we have examined the role of SSAT in the pathogenesis of toxic liver injury caused by carbon tetrachloride (CCl 4). The expression and activity of SSAT increase in the liver subsequent to CCl 4 administration. Furthermore, the early liver injury after CCl 4 treatment was significantly attenuated in hepatocyte-specific SSAT knockout mice (Hep-SSAT-Cko) compared with wild-type (WT) mice as determined by the reduced serum alanine aminotransferase levels, decreased hepatic lipid peroxidation, and less severe liver damage. Cytochrome P450 2e1 levels remained comparable in both genotypes, suggesting that SSAT deficiency does not affect the metabolism of CCl 4. Hepatocyte-specific deficiency of SSAT also modulated the induction of cytokines involved in inflammation and repair as well as leukocyte infiltration. In addition, Noxa and activated caspase 3 levels were elevated in the livers of WT compared with Hep-SSAT-Cko mice. Interestingly, the onset of cell proliferation was significantly more robust in the WT compared with Hep-SSAT Cko mice. The inhibition of polyamine oxidases protected the animals against CCl4-induced liver injury. Our studies suggest that while the abrogation of polyamine back conversion or inhibition of polyamine oxidation attenuate the early injury, they may delay the onset of hepatic regeneration. hepatotoxicity; carbon tetrachloride; polyamine POLYAMINES INTERACT WITH NUCLEIC acids and proteins and through these interactions play important roles in gene transcription, signal transduction, and cell proliferation (6,12,14,15,20). The cellular levels of polyamines are tightly regulated through import, export, synthesis and catabolism (Fig. 1). The initial step in polyamine synthesis is the decarboxylation of ornithine by ornithine decarboxylase (ODC) to form putrescine (Put). Sequential addition of aminopropyl residues to Put and spermidine (Spd) lead to the formation of Spd and spermine (Spm). Polyamines are degraded through their back conversion by Spm/Spd-N 1 -acetyltransferase (SSAT) and N 1 -acetylpolyamine oxidase (APAO) or by oxidation of Spm by Spm oxidase (SMO). Oxidation of acetylated Spm and Spd by APAO and Spm by SMO generates cytotoxic molecules such as H 2 O 2 and aldehydes (i.e., 3-aminopropanal and 3-acetoaminopropanal; Fig. 1).The expression and activity of SSAT increases in organs (e.g., liver, kidney, and brain) subjected to ischemia-reperfusion and septic and traumatic injuries (4,35,37,39). The ablation of the SSAT gene reduces the severity of renal and hepatic ischemia-reperfusion and endotoxin-induced renal injuries (35,37). Transgenic animals that express high levels of SSAT develop several pathologies, including skin lesions and pancreatitis (1,24,25). In vitro, expression of SSAT causes oxidative stress, DNA damage, cell cycle arrest, and apoptosis (7, 11). These results sugg...

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Contribution of polyamine oxidase to brain injury after trauma

Cited by 43 publications

References 21 publications

In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury

In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury

Elevated N¹‐Acetylspermidine Levels in Gerbil and Rat Brains After CNS Injury

Hepatocyte-specific ablation of spermine/spermidine-N¹-acetyltransferase gene reduces the severity of CCl₄-induced acute liver injury

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Contribution of polyamine oxidase to brain injury after trauma

Cited by 43 publications

References 21 publications

In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury

In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury

Elevated N1‐Acetylspermidine Levels in Gerbil and Rat Brains After CNS Injury

Hepatocyte-specific ablation of spermine/spermidine-N1-acetyltransferase gene reduces the severity of CCl4-induced acute liver injury

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Product

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Elevated N¹‐Acetylspermidine Levels in Gerbil and Rat Brains After CNS Injury

Hepatocyte-specific ablation of spermine/spermidine-N¹-acetyltransferase gene reduces the severity of CCl₄-induced acute liver injury