Effect of aging and oxidative/genotoxic stress on poly(ADP-ribose) polymerase-1 activity in rat brain.

Strosznajder, Robert P.; Jęśko, Henryk; Adamczyk, Agata

doi:10.18388/abp.2005_3406

Cited by 15 publications

(6 citation statements)

References 28 publications

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“…However, we ought to keep in mind that AIF after translocation to nucleus exerted endonuclease activity and is responsible for the DNA degradation into 50 kb fragments [ 65 ]. Our data indicated that C2-ceramide caused the AIF release from mitochondria, which was also observed in other experimental conditions by [ 21 – 23 , 37 , 60 , 65 ]. Our study showed that PARP-1 inhibition significantly protected SH-SY5Y against ceramide-induced cell death by reducing the level of ROS production, thus preventing the AIF release from the mitochondria and increasing the mRNA level of anti-apoptotic Bcl-2.…”

Section: Discussionsupporting

confidence: 89%

Ceramide in the Molecular Mechanisms of Neuronal Cell Death. The Role of Sphingosine-1-Phosphate

Czubowicz

Strosznajder

2014

Mol Neurobiol

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Ceramide and sphingosine-1-phosphate (S1P), two important bioactive sphingolipids, have been suggested as being key players in the pathology of Alzheimer's disease in inflammation and cancer. However, their role in the molecular mechanisms of neuronal death has not been fully elucidated. Our study indicated that ceramide significantly enhanced the level of free radicals and decreased the viability of the human neuroblastoma cell line (SH-SY5Y) through inhibition of the prosurvival PI3-K/Akt pathway. Ceramide also decreased anti-apoptotic (Bcl-2) and increased pro-apoptotic (Bax, Hrk) mRNA/protein levels. Concomitantly, our study indicated that ceramide induced poly(ADP-ribose) polymerase-1 (PARP-1) activation and accumulation of poly(ADP-ribose) PAR, a signalling molecule involved in mitochondria-nucleus cross-talk and mitochondria integrity. Ceramide treatment significantly decreased the level of apoptosis-inducing factor (AIF) in the mitochondria. The PARP-1 inhibitor (PJ-34) prevented AIF release from the mitochondria. In addition, our data showed that exogenously added S1P increased the viability of SH-SY5Y through the S1P (1,3) receptordependent mechanism. It was also revealed that the S1P and PARP-1 inhibitor (PJ-34) decreased oxidative stress, gene expression of the pro-apoptotic Hrk protein and up-regulated the anti-apoptotic Bcl-2 protein. Our data demonstrate that neuronal cell death evoked by ceramide is regulated by PARP/PAR/AIF and by S1P receptor signalling. In summary, our results suggest that PARP-1 inhibitor(s) and modulators of sphingosine-1-phosphate receptor(s) should be considered in potential therapeutic strategies directed at neurodegenerative diseases.

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Section: Discussionsupporting

confidence: 89%

Ceramide in the Molecular Mechanisms of Neuronal Cell Death. The Role of Sphingosine-1-Phosphate

Czubowicz

Strosznajder

2014

Mol Neurobiol

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“…According to the classical hypothesis (Zhang & Steiner, 1995) the free radical cascade that can be initiated with excessive liberation of NO leads to DNA damage that activates poly(ADP-ribose) polymerase (PARP-1). An enhancement of this enzyme activity was observed by us in aged brain (Strosznajder et al, 2005b). Massive single-or double strand breaks of DNA are responsible for PARP-1 overactivation.…”

Section: Introductionmentioning

confidence: 64%

“…The free radical-mediated damage of DNA causes activation of PARP-1 and depletion of βNAD + and may lead to a decrease of mitochondrial membrane potential and AIF release from mitochondria (Chiarugi & Moskowitz, 2002;Yu et al, 2002;Strosznajder et al 2005b).…”

mentioning

confidence: 99%

Molecular mechanism of PC12 cell death evoked by sodium nitroprusside, a nitric oxide donor.

Pytlowany

Strosznajder²,

Jęśko³

et al. 2008

Acta Biochim Pol

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Nitric oxide (NO) is a potent extracellular and intracellular physiological messenger. However, NO liberated in excessive amounts can be involved in macromolecular and mitochondrial damage in brain aging and in neurodegenerative disorders. The molecular mechanism of its neurotoxic action is not fully understood. Our previous data indicated involvement of NO in the release of arachidonic acid (AA), a substrate for cyclo- and lipoxygenases (COX and LOX, respectively). In this study we investigated biochemical processes leading to cell death evoked by an NO donor, sodium nitroprusside (SNP). We found that SNP decreased viability of pheochromocytoma (PC12) cells in a concentration- and time-dependent manner. SNP at 0.1 mM caused a significant increase of apoptosis-inducing factor (AIF) protein level in mitochondria. Under these conditions 80% of PC12 cells survived. The enhancement of mitochondrial AIF level might protect most of PC12 cells against death. However, NO released from 0.5 mM SNP induced massive cell death but had no effect on protein level and localization of AIF and cytochrome c. Caspase-3 activity and poly(ADP-ribose) polymerase-1 (PARP-1) protein levels were not changed. However, PARP activity significantly decreased in a time-dependent manner. Inhibition of both COX isoforms and of 12/15-LOX significantly lowered the SNP-evoked cell death. We conclude that AIF, cytochrome c and caspase-3 are not responsible for the NO-mediated cell death evoked by SNP. The data demonstrate that NO liberated in excess decreases PARP-1 activity. Our results indicate that COX(s) and LOX(s) are involved in PC12 cell death evoked by NO released from its donor, SNP.

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“…Recent studies regarding PARP-1 in brain aging appear to support the hypothesis that decreased PARP-1 activity in response to genotoxic insults may contribute to brain aging. It was reported that PARP-1 is not activated by excessive oxidative/genotoxic stress in aged hippocampus, in contrast to a significant increase in PARP-1 activity in adults (268). There are also age-related alterations of PAR synthesis in rat cerebellum, including reduced PARP-1 activation in response to enzymatic DNA cleavage and cell type-specific loss of poly(ADP-ribosyl)ation capacity in granule cell layer and Purkinje cells in vivo (269).…”

Section: Roles Of Parps In Brain Agingmentioning

confidence: 97%

NAD+ and NADH in brain functions, brain diseases and brain aging

Ying¹

2007

Front Biosci

109

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Numerous studies have suggested that NAD+ and NADH mediate multiple major biological processes, including calcium homeostasis, energy metabolism, mitochondrial functions, cell death and aging. In particular, NAD+ and NADH have emerged as novel, fundamental regulators of calcium homeostasis. It appears that most of the components in the metabolic pathways of NAD+ and NADH, including poly(ADP-ribose), ADP-ribose, cyclic ADP-ribose, O-acetyl-ADP-ribose, nicotinamide and kynurenine, can produce significant biological effects. This exquisiteness of NAD+ and NADH metabolism could epitomize the exquisiteness of life, through which we may grasp the intrinsic harmony life has evolved to produce. The exquisiteness also suggests a central regulatory role of NAD+ and NADH in life. It is tempted to propose that NAD+ and NADH, together with ATP and Ca2+, constitute a Central Regulatory Network of life. Increasing evidence has also suggested that NAD+ and NADH play important roles in multiple biological processes in brains, such as neurotransmission and learning and memory. NAD+ and NADH may also mediate brain aging and the tissue damage in various brain illnesses. Our latest studies have suggested that NADH can be transported across the plasma membranes of astrocytes, and that NAD+ administration can markedly decrease ischemic brain injury. Based on this information, it is proposed that NAD+ and NADH are fundamental mediators of brain functions, brain senescence and multiple brain diseases. Because numerous properties of NAD+ and NADH remain unclear, future studies regarding NAD+ and NADH may expose some fundamental mechanisms underlying brain functions, brain pathologies and brain aging.

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Effect of aging and oxidative/genotoxic stress on poly(ADP-ribose) polymerase-1 activity in rat brain.

Cited by 15 publications

References 28 publications

Ceramide in the Molecular Mechanisms of Neuronal Cell Death. The Role of Sphingosine-1-Phosphate

Ceramide in the Molecular Mechanisms of Neuronal Cell Death. The Role of Sphingosine-1-Phosphate

Molecular mechanism of PC12 cell death evoked by sodium nitroprusside, a nitric oxide donor.

NAD+ and NADH in brain functions, brain diseases and brain aging

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