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Involvement of poly(ADP-ribose) polymerase in paraptotic cell death of D. discoideum

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Abstract

Paraptosis is mediated by several proteins, poly(ADP-ribose) polymerase being one of them. D. discoideum lacks caspases thus providing a better system to dissect out the role of PARP in paraptosis. The cell death phenotype in unicellular eukaryote, D. discoideum is similar to the programmed cell death phenotype of multicellular animals. However, the events downstream to the death signal of PCD in D. discoideum are yet to be understood. Our results emphasize that oxidative stress in D. discoideum lacking caspases leads to PARP activation, mitochondrial membrane potential changes, followed by the release of apoptosis inducing factor from mitochondria. AIF causes large scale DNA fragmentation, a hallmark feature of paraptosis. The role of PARP in paraptosis is reiterated via PARP inhibition by benzamide, PARG inhibition by gallotannin and PARP down-regulation, which delays paraptosis. PARP, PARG and AIF interplay is quintessential in paraptosis of D. discoideum. This is the first report to establish the involvement of PARP in the absence of caspase activity in D. discoideum which could be of evolutionary significance and gives a lead to understand the caspase independent paraptotic mechanism in higher organisms.

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Abbreviations

PCD:

Programmed cell death

PARP:

Poly(ADP-ribose) polymerase

PARG:

Poly(ADP-ribose) glycohydrolase

AIF:

Apoptosis inducing factor

MMP:

Mitochondrial membrane potential

ROS:

Reactive oxygen species

H2O2 :

Cumene H2O2

PS:

Phosphatidylserine

PI:

Propidium iodide

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Acknowledgments

RB thanks the Department of Biotechnology, New Delhi (BT/PR9496/BRB/10/562/2007) and Department of Science and Technology, New Delhi (SR/SO/BB-03/2010) for research support. JR thanks Council Scientific Research, New Delhi for awarding JRF/SRF. We thank DBT-MSUB-ILSPARE program for providing the FACS and Confocal facilities. We also thank Dr. Shweta Saran for generous gift of vectors. Our sincere thanks are to Ms. Bandhana Katoch from M.S. University of Baroda, Vadodara; Prof. V. Nanjundiah and Dr. Ritwick Sarwarkar from Indian Institute of Science, Bangalore for their help in standardization of the fluorescence techniques.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390 002, Gujarat, India

    Jyotika Rajawat, Hina Mir, Tina Alex & Rasheedunnisa Begum

  2. Institute of Science, Nirma University, Ahmedabad, 382 481, Gujarat, India

    Sonal Bakshi

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  1. Jyotika Rajawat
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Correspondence to Rasheedunnisa Begum.

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Rajawat, J., Mir, H., Alex, T. et al. Involvement of poly(ADP-ribose) polymerase in paraptotic cell death of D. discoideum . Apoptosis 19, 90–101 (2014). https://doi.org/10.1007/s10495-013-0920-9

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