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Activation of cell death mediated by apoptosis-inducing factor due to the absence of poly(ADP-ribose) glycohydrolase.
Biochemistry. 2011 Apr 12; 50(14):2850-9.B

Abstract

We previously demonstrated that the absence of poly(ADP-ribose) glycohydrolase (PARG) led to increased cell death following DNA-damaging treatments. Here, we investigated cell death pathways following UV treatment. Decreased amounts of PARG-null embryonic trophoblast stem (TS) cells were observed following doses of 10-100 J/m2 as compared to wild-type cells. In wild-type cells, caspase-cleaved poly(ADP-ribose) polymerase-1 (PARP-1) and activated caspase-3 were detected 12-24 h after UV treatment. Surprisingly, both were detected at decreased levels only after 24 h in PARG-null TS cells, indicating a decreased level and delayed presence of caspase-mediated events. Further, a time- and dose-dependent accumulation of poly(ADP-ribose) (PAR) levels after UV was observed in PARG-null TS cells and not in wild-type cells. Determination of the levels of nicotinamide adenine dinucleotide (NAD+), the substrate for PAR synthesis and a coenzyme in cellular redox reactions, demonstrated a UV dose-dependent decrease in the level of NAD+ in wild-type cells, while NAD+ levels in PARG-null TS cells remained at higher levels. This indicates no depletion of NAD+ in PARG-null TS cells following increased levels of PAR. Lastly, cell death mediated by apoptosis-inducing factor (AIF) was analyzed because of its dependence on increased PAR levels. The results demonstrate nuclear AIF translocation only in PARG-null TS cells, which demonstrates the presence of AIF-mediated cell death. Herein, we provide compelling evidence that the absence of PARG leads to decreased caspase-3 activity and the specific activation of AIF-mediated cell death. Therefore, the absence of PARG may provide a strategy for specifically inducing an alternative apoptotic pathway.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, Washington 99164, United States.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21366272

Citation

Zhou, Yiran, et al. "Activation of Cell Death Mediated By Apoptosis-inducing Factor Due to the Absence of poly(ADP-ribose) Glycohydrolase." Biochemistry, vol. 50, no. 14, 2011, pp. 2850-9.
Zhou Y, Feng X, Koh DW. Activation of cell death mediated by apoptosis-inducing factor due to the absence of poly(ADP-ribose) glycohydrolase. Biochemistry. 2011;50(14):2850-9.
Zhou, Y., Feng, X., & Koh, D. W. (2011). Activation of cell death mediated by apoptosis-inducing factor due to the absence of poly(ADP-ribose) glycohydrolase. Biochemistry, 50(14), 2850-9. https://doi.org/10.1021/bi101829r
Zhou Y, Feng X, Koh DW. Activation of Cell Death Mediated By Apoptosis-inducing Factor Due to the Absence of poly(ADP-ribose) Glycohydrolase. Biochemistry. 2011 Apr 12;50(14):2850-9. PubMed PMID: 21366272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of cell death mediated by apoptosis-inducing factor due to the absence of poly(ADP-ribose) glycohydrolase. AU - Zhou,Yiran, AU - Feng,Xiaoxing, AU - Koh,David W, Y1 - 2011/03/21/ PY - 2011/3/4/entrez PY - 2011/3/4/pubmed PY - 2011/8/5/medline SP - 2850 EP - 9 JF - Biochemistry JO - Biochemistry VL - 50 IS - 14 N2 - We previously demonstrated that the absence of poly(ADP-ribose) glycohydrolase (PARG) led to increased cell death following DNA-damaging treatments. Here, we investigated cell death pathways following UV treatment. Decreased amounts of PARG-null embryonic trophoblast stem (TS) cells were observed following doses of 10-100 J/m2 as compared to wild-type cells. In wild-type cells, caspase-cleaved poly(ADP-ribose) polymerase-1 (PARP-1) and activated caspase-3 were detected 12-24 h after UV treatment. Surprisingly, both were detected at decreased levels only after 24 h in PARG-null TS cells, indicating a decreased level and delayed presence of caspase-mediated events. Further, a time- and dose-dependent accumulation of poly(ADP-ribose) (PAR) levels after UV was observed in PARG-null TS cells and not in wild-type cells. Determination of the levels of nicotinamide adenine dinucleotide (NAD+), the substrate for PAR synthesis and a coenzyme in cellular redox reactions, demonstrated a UV dose-dependent decrease in the level of NAD+ in wild-type cells, while NAD+ levels in PARG-null TS cells remained at higher levels. This indicates no depletion of NAD+ in PARG-null TS cells following increased levels of PAR. Lastly, cell death mediated by apoptosis-inducing factor (AIF) was analyzed because of its dependence on increased PAR levels. The results demonstrate nuclear AIF translocation only in PARG-null TS cells, which demonstrates the presence of AIF-mediated cell death. Herein, we provide compelling evidence that the absence of PARG leads to decreased caspase-3 activity and the specific activation of AIF-mediated cell death. Therefore, the absence of PARG may provide a strategy for specifically inducing an alternative apoptotic pathway. SN - 1520-4995 UR - https://www.unboundmedicine.com/medline/citation/21366272/Activation_of_cell_death_mediated_by_apoptosis_inducing_factor_due_to_the_absence_of_poly_ADP_ribose__glycohydrolase_ L2 - https://doi.org/10.1021/bi101829r DB - PRIME DP - Unbound Medicine ER -