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NAD+ and NADH in Cellular Functions and Cell Death

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Mariano Perez
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144 views

NAD+ and NADH in Cellular Functions and Cell Death

science

Uploaded by

Mariano Perez
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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NAD+ and NADH in cellular functions and cell death.

Ying W.
Source
Department of Neurology, University of California, San Francisco Veterans Affairs
Medical Center, San Francisco, CA 94121, USA. [email protected]

Abstract
Increasing evidence has indicated that NAD+ and NADH play critical roles
not only in energy metabolism, but also in cell death and various cellular
functions including regulation of calcium homeostasis and gene expression.
It has also been indicated that NAD+ and NADH are mediators of multiple
major biological processes including aging. NAD+ and NADH produce the
biological effects by regulating numerous NAD+/NADH-dependent
enzymes, including dehydrogenases, poly(ADP-ribose) polymerases, Sir2
family proteins (sirtuins), mono(ADP-ribosyl)transferases, and ADP-ribosyl
cyclases. Of particular interest, NAD+-dependent generation of ADP-ribose,
cyclic ADP-ribose and O-acetyl-ADP-ribose can mediate calcium
homeostasis by affecting TRPM2 receptors and ryanodine receptors; and
sirtuins and PARPs appear to play key roles in aging, cell death and a
variety of cellular functions. It has also been indicated that NADH and
NAD+ can be transported across plasma membranes of cells, and that
extracellular NAD+ may be a new signaling molecule. Our latest studies
have shown that intranasal NAD+ administration can profoundly decrease
ischemic brain damage. These new pieces of information have
fundamentally changed our understanding about NAD+ and NADH,
suggesting novel paradigms about the metabolism and biological activities
of NAD+ and NADH. Based on this information, it is tempted to
hypothesize that NAD+ and NADH, together with ATP and Ca2+, may be
four most fundamental components in life, which can significantly affect
nearly all major biological processes. Future studies on NAD+ and NADH
may not only elucidate some fundamental mysteries in biology, but also
provide novel insights for interfering aging and many disease processes.
PMID: 16720381 [PubMed - indexed for MEDLINE]

NAD+ and NADH in brain functions, brain diseases and


brain aging.
Ying W.
Source
Department of Neurology, University of California at San Francisco and San Francisco
Veterans Affairs Medical Center, San Francisco, CA 94121, USA. [email protected]

Abstract
Numerous studies have suggested that NAD+ and NADH mediate multiple
major biological processes, including calcium homeostasis, energy
metabolism, mitochondrial functions, cell death and aging. In particular,
NAD+ and NADH have emerged as novel, fundamental regulators of
calcium homeostasis. It appears that most of the components in the
metabolic pathways of NAD+ and NADH, including poly(ADP-ribose),
ADP-ribose, cyclic ADP-ribose, O-acetyl-ADP-ribose, nicotinamide and
kynurenine, can produce significant biological effects. This exquisiteness
of NAD+ and NADH metabolism could epitomize the exquisiteness of life,
through which we may grasp the intrinsic harmony life has evolved to
produce. The exquisiteness also suggests a central regulatory role of
NAD+ and NADH in life. It is tempted to propose that NAD+ and NADH,
together with ATP and Ca2+, constitute a Central Regulatory Network of
life. Increasing evidence has also suggested that NAD+ and NADH play
important roles in multiple biological processes in brains, such as
neurotransmission and learning and memory. NAD+ and NADH may also
mediate brain aging and the tissue damage in various brain illnesses. Our
latest studies have suggested that NADH can be transported across the
plasma membranes of astrocytes, and that NAD+ administration can
markedly decrease ischemic brain injury. Based on this information, it is
proposed that NAD+ and NADH are fundamental mediators of brain
functions, brain senescence and multiple brain diseases. Because
numerous properties of NAD+ and NADH remain unclear, future studies
regarding NAD+ and NADH may expose some fundamental mechanisms
underlying brain functions, brain pathologies and brain aging.
PMID: 17127427 [PubMed - indexed for MEDLINE]

NAD+/NADH and NADP+/NADPH in cellular functions


and cell death: regulation and biological consequences.
Ying W.
Source
Department of Neurology, University of California at San Francisco, San Francisco,
California 94121, USA. [email protected]

Abstract
Accumulating evidence has suggested that NAD (including NAD+ and
NADH) and NADP (including NADP+ and NADPH) could belong to the
fundamental common mediators of various biological processes, including
energy metabolism, mitochondrial functions, calcium homeostasis,
antioxidation/generation of oxidative stress, gene expression,
immunological functions, aging, and cell death: First, it is established that
NAD mediates energy metabolism and mitochondrial functions; second,
NADPH is a key component in cellular antioxidation systems; and NADHdependent reactive oxygen species (ROS) generation from mitochondria
and NADPH oxidase-dependent ROS generation are two critical
mechanisms of ROS generation; third, cyclic ADP-ribose and several other
molecules that are generated from NAD and NADP could mediate calcium
homeostasis; fourth, NAD and NADP modulate multiple key factors in cell
death, such as mitochondrial permeability transition, energy state,
poly(ADP-ribose) polymerase-1, and apoptosis-inducing factor; and fifth,
NAD and NADP profoundly affect aging-influencing factors such as
oxidative stress and mitochondrial activities, and NAD-dependent sirtuins
also mediate the aging process. Moreover, many recent studies have
suggested novel paradigms of NAD and NADP metabolism. Future
investigation into the metabolism and biological functions of NAD and
NADP may expose fundamental properties of life, and suggest new
strategies for treating diseases and slowing the aging process.
PMID: 18020963 [PubMed - indexed for MEDLINE]

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