Regulation of DNAS1L3 Endonuclease Activity by Poly(ADP-ribosyl)ation during Etoposide-induced Apoptosis

Boulares, A. Hamid; Zoltoski, Anna J.; Contreras, Francisco; Yakovlev, Alexander G.; Yoshihara, Koichiro; Smulson, Mark E.

doi:10.1074/jbc.m107738200

Cited by 61 publications

(50 citation statements)

References 47 publications

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“…31 It has been reported that, at early stages of apoptosis, DNaseY can be inactivated by PARP-1 through the poly-ADPribosylation mechanism. 18,19 Here we found a significant upregulation of PARP-1 in the DNaseY-overexpressing cells (Figure 11a). Therefore, it is possible that PARP-1 acts both as a sensor to detect ssb and at the same time to synthesize negatively charged ADP-ribose polymers to inhibit the endonuclease that creates them.…”

Section: Discussionmentioning

confidence: 66%

“…Therefore, it is possible that PARP-1 acts both as a sensor to detect ssb and at the same time to synthesize negatively charged ADP-ribose polymers to inhibit the endonuclease that creates them. 20,32 In the execution phase of apoptosis, PARP-1 is cleaved and inactivated by caspaselike proteases relieving inhibition of DNaseY; 18,19 however, the inactivation of PARP-1 may not be sufficient to fully unleash the activity of DNaseY. The cytoplasmic changes, that is, alterations in signalling pathways and cytoskeletal changes, might also be required to accomplish this.…”

Section: Discussionmentioning

confidence: 99%

“…This negative regulation of DNaseY may be reversed upon the cleavage and inactivation of PARP-1 by a caspase-3 like protease, followed by reactivation of DNaseY by PAR glycohydrolase. 18,19 PARP-1 has long been considered a molecular 'nick sensor' that is activated at the sites of ssb and synthesizes negatively charged poly-ADP-ribose. [20][21][22] Its physical interaction with the base excision repair protein, X-ray repair cross complementing 1 (XRCC1), confirms that PARP-1 is a member of a multiprotein complex involved in the DNA polymerase b, XRCC1 and DNA ligase 3 (Polb-XRCC1-Lig3) repair pathway.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of DNaseY activity by actinin-α4 during apoptosis

et al. 2004

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DNaseY, a Ca 2 þ -and Mg 2 þ -dependent endonuclease, has been implicated in apoptotic DNA degradation; however, the molecular mechanisms controlling its involvement in this process have not been fully elucidated. We have obtained evidence from yeast two-hybrid screening and coimmunoprecipitation experiments that DNaseY interacted physically with actinin-a4 and this interaction significantly enhanced its endonuclease activity. Accordingly, simultaneous overexpression of both proteins in PC12 cells dramatically increased the rate of apoptosis in response to teniposide' VM26. However, overexpression of DNaseY alone neither triggered apoptosis nor facilitated cell death in response to VM26 or serum deprivation. Instead, the overexpression of DNaseY increased the production of single-strand DNA breaks and evoked a profound upregulation of DNA repair pathways. Taken together, our results point to a novel regulatory mechanism of DNaseY activity and offer an explanation for why cells must first cleave key DNA repair and replication proteins before the successful execution of apoptosis.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of DNaseY activity by actinin-α4 during apoptosis

et al. 2004

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“…In addition to the known beneficial changes in the MPTP by pyruvate, the redox sensitive antiapoptotic protein Bcl-Xl also blocks the release of cytochrome c. Decreasing the release of cytochrome c is important because cytochrome c irreversibly commits the cell to death by activating caspase 3 and the degradation phase of apoptosis. Activation of caspase 3 has been linked to the proteolytic cleavage of cellular substrates including PARP, a strong indicator of apoptosis (6,13,35). Although some studies have shown that Bcl2 and Bcl-Xl are equally effective in preventing apoptosis, others have suggested that overexpression of Bcl-Xl is more important in the protection of apoptosis induced by ischemia-reperfusion (8,46).…”

Section: Discussionmentioning

confidence: 99%

Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine

Mongan

Capacchione

West

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine. Am J Physiol Heart Circ Physiol 283: H1634-H1644, 2002. First published June 20, 2002 10.1152/ ajpheart.01073.2001.-Previous studies have shown that the liver is the first organ to display signs of injury during hemorrhagic shock. We examined the mechanism by which pyruvate can prevent liver damage during hemorrhagic shock in swine anesthetized with halothane. Thirty minutes after the induction of a 240-min controlled arterial hemorrhage targeted at 40 mmHg, hypertonic sodium pyruvate (0.5 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) was infused to achieve an arterial concentration of 5 mM. The volume and osmolality effects of pyruvate were matched with 10% saline (HTS) and 0.9% saline (NS). Although the peak hemorrhage volume increased significantly in both the pyruvate and HTS group, only the pyruvate treatment was effective in delaying cardiovascular decompensation. In addition, pyruvate effectively maintained the NADH/NAD redox state, as evidenced by increased microdialysate pyruvate levels and a significantly lower lactateto-pyruvate ratio. Pyruvate also prevented the loss of intracellular antioxidants (GSH) and a reduction in the GSH-to-GSSG ratio. These beneficial effects on the redox environment decreased hepatic cellular death by apoptosis. Pyruvate significantly increased the ratio of Bcl-Xl (antiapoptotic molecule)/Bax (proapoptotic molecule), prevented the release of cytochrome c from mitochondria, and decreased the fragmentation of caspase 3 and poly(ADP ribose) polymerase (DNA repair enzyme). These beneficial findings indicate that pyruvate infused 30 min after the onset of severe hemorrhagic shock is effective in maintaining the redox environment, preventing the loss of the key antioxidant GSH, and decreasing early apoptosis indicators. glutathione; redox state; caspases DESPITE ADVANCES IN THE EARLY CARE of trauma victims over the past two decades, multiple organ failure (MOF) continues to be a major factor in the morbidity and mortality that occurs after resuscitation from hemorrhagic shock (16). While there are numerous factors that influence the development of MOF, there is increasing evidence that hepatic dysfunction plays a central role (21,24,42,43). Experimental studies have shown that despite acute aggressive resuscitation, there is a consistent depression in microvascular blood flow that results in hypoperfusion and progressive hepatic dysfunction (32,42,43). This suggests that despite the restoration of global oxygen delivery, additional pharmacological therapies are needed to prevent or reverse ongoing hepatotoxicity. However, the precise mechanisms of hepatocellular dysfunction after severe hemorrhagic shock are not well defined. Some investigators have shown that the reduction in immunological mediators, such as tumor necrosis factor-␣, improves outcome indicators (23,41). Others have shown that there is severe hepatic energy depletion during hemorrhagic shock and that improvement in the hepatoce...

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“…We previously made a DFF45 mutant (Ϫ͞Ϫ) mouse and found that DNA fragmentation in DFF45 Ϫ/Ϫ thymocytes exposed to various apoptotic stimuli is profoundly impaired (11)(12)(13)(14). Moreover, DFF45 Ϫ/Ϫ thymocytes and mouse embryonic fibroblasts (MEFs) exposed to several apoptotic agents are partially resistant to apoptosis and chromatin condensation (11,15,16). DFF45 Ϫ/Ϫ mice also exhibit reduced natural killer T cell death after certain viral infections (17) and are more resistant to neuronal cell death after excessive excitatory stimulation, compared with wild-type mice (18).…”

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confidence: 99%

Endonuclease G is required for early embryogenesis and normal apoptosis in mice

Zhang

Dong

et al. 2003

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

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Endonuclease G (EndoG) is a nuclear-encoded mitochondrial protein reported to be important for both nuclear DNA fragmentation during apoptosis and mitochondrial DNA replication. To evaluate the in vivo function of EndoG, we have investigated the effects of EndoG deficiency in cells and mice. We found that EndoG homozygous mutant embryos die between embryonic days 2.5 and 3.5. Mitochondrial DNA copy numbers in ovulated oocytes from EndoG heterozygous mutant and wild-type mice are similar, suggesting that EndoG is involved in a cellular function unrelated to mitochondrial DNA replication. Interestingly, we found that cells from EndoG heterozygous mutant mice exhibit increased resistance to both tumor necrosis factor ␣-and staurosporine-induced cell death. Moreover, spontaneous cell death of spermatogonia in EndoG heterozygous mutant mice is significantly reduced compared with wild-type mice. DNA fragmentation is also reduced in EndoG ؉͞؊ thymocytes and splenocytes compared with wild-type cells, as well as in EndoG ؉͞؊ thymus in vivo compared with that of the wild-type mice, on activation of apoptosis. These findings indicate that EndoG is essential during early embryogenesis and plays a critical role in normal apoptosis and nuclear DNA fragmentation.

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Regulation of DNAS1L3 Endonuclease Activity by Poly(ADP-ribosyl)ation during Etoposide-induced Apoptosis

Cited by 61 publications

References 47 publications

Regulation of DNaseY activity by actinin-α4 during apoptosis

Regulation of DNaseY activity by actinin-α4 during apoptosis

Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine

Endonuclease G is required for early embryogenesis and normal apoptosis in mice

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