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

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Title Statement NAD+ supplementation reverses the oxidative stress induced PARP1 signalling in <em>D. discoideum</em>
 
Added Entry - Uncontrolled Name Rajawat, Jyotika
Vohra, Iqbal
Mir, Hina
Begum, Rasheedunnisa
 
Uncontrolled Index Term NAD+ supplementation; PARP1; paraptotic cell death; necrotic cell death; metabolite; pharmacological inhibition
 
Summary, etc. 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 <em>D. discoideum</em>. 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 <em>D. discoideum</em>. 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 <em>D. discoideum</em> cell death. Moreover, NAD+ supplementation could be a beneficial approach in aging and age-related disorders mediated by PARP1
 
Publication, Distribution, Etc. Indian Journal of Biochemistry and Biophysics (IJBB)
2022-10-04 16:34:31
 
Electronic Location and Access application/pdf
http://op.niscair.res.in/index.php/IJBB/article/view/60730
 
Data Source Entry Indian Journal of Biochemistry and Biophysics (IJBB); IJBB Vol. 59 (10) [October 2022]
 
Language Note en