Neuronal and Glial Responses to Polyamines in the Ischemic Brain

Abstract

The polyamines, putrescine, spermidine and spermine are present in most living cells, with the essentiality for normal cell function, cellular growth and differentiation. In the mammalian brain, polyamines are also present at relatively high concentrations with different regional distribution profiles. Cerebral ischemia is a leading cause of disability and mortality in humans, and believed to yield a cascade of cytotoxic molecules responsible for the death of viable cells in the brain. Polyamines have been implicated in the pathogenesis of ischemic brain damage. For example, polyamine biosynthesis is increased after the onset of cerebral ischemia through an induction of ornithine decarboxylase, a key enzyme in the polyamine biosynthetic pathway. The administration of a drug that inhibits ornithine decarboxylase activity prevents the development of ischemic brain damage, suggesting a critical role of the accumulation of polyamines in the ischemic brain in the pathogenesis of stroke. Both spermine and spermidine are linked to the development of glutamate-mediated neurotoxicity, for they can bind to the N-methyl-D-aspartate (NMDA)-sensitive subtype of glutamate receptors to potentiate cellular responses to glutamate. Moreover, polyamines are metabolized by polyamine oxidases after acetylation to produce different cytotoxic aldehydes and reactive oxygen species such as hydrogen peroxide, which possibly damage proteins, DNA and lipids. Polyamines have been extensively studied in the ischemic brain, particularly with respect to neuronal responses such as NMDA receptor-mediated excitotoxicity. However, little is known about glial responses to polyamines in the ischemic brain to date. In this review, we would summarize previous studies related to neuronal and glial responses to polyamines in the ischemic brain.

Arginase 1 Regulation of Nitric Oxide Production Is Key to Survival of Trophic Factor-Deprived Motor Neurons

“…Polyamines, small molecules with regularly spaced cation charges, are known to influence a diversity of biological activities including cell proliferation, regeneration, and death (Lange et al, 2004;Seiler and Raul, 2005;Takano et al, 2005). Arginase can increase polyamine synthesis by catalyzing the hydrolysis of arginine to ornithine and urea.…”

Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy

“…Alterations in polyamine metabolism have been demonstrated to be involved in the pathogenesis of Alzheimer's disease [25], Parkinson's disease [26], cancer [27–29], traumatic brain injury [30], and ischemic brain damage [31,32]. Activation of polyamine oxidases (PAOs) including spermine oxidase (SMO) and acetyl polyamine oxidase (APAO) leads to formation of cytotoxic aldehydes, acrolein and hydrogen peroxide (H 2 O 2 ), which can damage DNA, RNA, proteins and lipids [33].…”

CRHR1-dependent effects on protein expression and posttranslational modification in AtT-20 cells

“…In the acute incubation experiment the protein with the lower pI decreased in intensity during the course of incubation whereas the protein with the higher pI increased. The enzyme's products, the natural polyamine cations spermidine and spermine, have multiple functions in cell growth and maintenance of cell viability (Seiler and Raul, 2005) as well as neuroprotection and neurotoxicity (Janne et al, 2005;Takano et al, 2005). In the mammalian brain, polyamines are present at high concentrations and their biosynthesis is induced by stressful stimuli such as physical, emotional or hormonal stressors suggesting that an appropriate regulation of this polyamine stress response might be relevant for neuronal function and behavioral adaptation to stress (Gilad and Gilad, 2003).…”