NAD+ supplementation reverses the oxidative stress induced PARP1 signalling in <em>D. discoideum</em>
Online Publishing @ NISCAIR
View Archive InfoField | Value | |
Authentication Code |
dc |
|
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 |
|