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Signaling interplay between PARP1 and ROS regulates stress-induced cell death and developmental changes in Dictyostelium discoideum.

Abstract：

:Poly (ADP-ribose) polymerase-1 (PARP1) is a DNA damage sensor that gets activated in proportion to the damage, helping cells to determine whether to repair the damage or initiate cell death processes. We have previously shown PARP1's significance in the developmental processes of Dictyostelium discoideum in addition to its role in oxidative stress and UV-C stress induced cell death. In this study, we show the significance of ROS in PARP1 mediated responses of D. discoideum under different stress conditions. Interestingly, our results suggest differential kinetics of PARP1 activation and implications of ROS in starvation and cadmium induced cell death events. Increased accumulation of Poly (ADP-ribose), a product of PARP activation, could be detected within minutes post cadmium stress, whereas PARP1 activation was only a later event with starvation. Starvation induced PARP1 activation was supported by the depletion of ATP and NAD+, while PARP inhibitor confers protective effect during starvation. During starvation, cell death is induced in two phases, a primary ROS driven PARP1 independent early necrotic phase followed by a PARP1 driven ROS dependent paraptotic phase; both of which comprise mitochondrial changes. Cadmium (Cd) exerted a dose-dependent effect on cell death; a low dose of 0.2 mM Cd led to paraptosis and a higher dose of 0.5 mM Cd led to necrosis in D. discoideum cells within 24 h. Interestingly, glutathione (GSH) exposure could rescue cells from Cd stress mediated cell death. Besides unicellular cell death, the developmental arrest induced by cadmium and oxidative stress could be rescued by reinstating the redox equilibrium using GSH. In conclusion, we underscore the significant link between PARP1 and ROS in regulating the process of cell death and development in D. discoideum.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Mir H,Rajawat J,Vohra I,Vaishnav J,Kadam A,Begum R

doi

10.1016/j.yexcr.2020.112364

subject

Has Abstract

pub_date

2020-12-15 00:00:00

pages

112364

issue

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(20)30617-0

journal_volume

397

pub_type

杂志文章

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Signaling interplay between PARP1 and ROS regulates stress-induced cell death and developmental changes in Dictyostelium discoideum.