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NAD<sup>+ </sup> supplementation reverses the oxidative stress induced PARP1 signalling in D. discoideum

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Title NAD+ supplementation reverses the oxidative stress induced PARP1 signalling in D. discoideum
 
Creator Rajawat, Jyotika
Vohra, Iqbal
Mir, Hina
Begum, Rasheedunnisa
 
Subject Metabolite
NAD+ supplementation
Necrotic cell death
Paraptotic cell death
PARP1
Pharmacological inhibition
 
Description 977-984
Increased oxidative stress leads to cell death by inducing DNA damage, PARP activation and energy depletion in age related disorders which are a growing concern due to increased life expectancy. Indeed, cellular NAD+ levels, depletion of which is one of the consequences of overactive PARP, also decline with age. We previously showed rescue in oxidative stress induced paraptotic and necrotic cell death by PARP1 inhibition in D. discoideum. Inhibition of PARP1 activity prevented cellular depletion of its substrate NAD+. To understand the significance of NAD+ depletion in PARP1 mediated oxidative stress induced cell death, exogenous addition of NAD+ was done. Addition of NAD+ prevented PARP1 mediated oxidative stress induced cell death at low doses upto 10 mM NAD+, nevertheless led to an anticipated increase in PARP1 activity. NAD+ significantly prevented oxidative stress induced cell death in D. discoideum. Exogenous NAD+ averted depletion of cellular NAD+ and mitochondrial membrane potential changes that were triggered by oxidative stress, without getting affected by the elevated ROS levels. Altogether, this study ascertains that NAD+ replenishment overcomes cadmium or H2O2 induced cell death by preventing cellular energy collapse incited by PARP1 activation. Thus, our results explicitly demonstrate that PARP1 overactivation led NAD+ depletion but not PARP1 activity per se is of consequential significance in causing oxidative stress induced D. discoideum cell death. Moreover, NAD+ supplementation could be a beneficial approach in aging and age-related disorders mediated by PARP1.
 
Date 2022-10-06T09:31:06Z
2022-10-06T09:31:06Z
2022-10
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://nopr.niscpr.res.in/handle/123456789/60638
https://doi.org/10.56042/ijbb.v59i10.60730
 
Language en
 
Publisher NIScPR-CSIR,India
 
Source IJBB Vol.59(10) [Oct 2022]