Pathophysiological aspects of cellular pyridine nucleotide metabolism

Focus on the vascular endothelium. Review

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In recent years, pyridine nucleotides NAD(H) and NADP(H) have been established as an important molecules in physiological and pathophysiological signaling and cell injury pathways. Protein modification is catalyzed by ADP-ribosyl transferases that attach the ADP-ribose moiety of NAD+ to specific aminoacid residues of the acceptor proteins, with significant changes in the function of these acceptors. Mono(ADP-ribosyl)ation reactions have been implicated to play a role both in physiological responses and in cellular responses to bacterial toxins. Cyclic ADP-ribose formation also utilizes NAD+ and primarily serves as physiological, signal transduction mechanisms regulating intracellular calcium homeostasis. In pathophysiological conditions associated with oxidative stress (such as various forms of inflammation and reperfusion injury), activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) occurs, with subsequent, substantial fall in cellular NAD+ and ATP levels, which can determine the viability and function of the affected cells. In addition, NADPH oxidases can significantly affect the balance and fate of NAD+ and NADP in oxidatively stressed cells and can facilitate the generation of various positive feedback cycles of injury. Under severe oxidant conditions, direct oxidative damage to NAD + has also been reported. The current review focuses on PARP and on NADPH oxidases, as pathophysiologically relevant factors in creating disturbances in the cellular pyridine nucleotide balance. A separate section describes how these mechanisms apply to the pathogenesis of endothelial cell injury in selected cardiovascular pathophysiological conditions.

Original languageEnglish (US)
Pages (from-to)175-193
Number of pages19
JournalActa Physiologica Hungarica
Volume90
Issue number3
DOIs
StatePublished - 2003
Externally publishedYes

Fingerprint

Vascular Endothelium
NAD
Nucleotides
Poly(ADP-ribose) Polymerases
NADPH Oxidase
NADP
Adenosine Diphosphate
Wounds and Injuries
Cyclic ADP-Ribose
ADP Ribose Transferases
Bacterial Toxins
Enzyme Activation
Reperfusion Injury
Oxidants
pyridine
Signal Transduction
Proteins
Oxidative Stress
Homeostasis
Endothelial Cells

Keywords

  • DNA
  • Endothelium
  • Free radicals
  • Inflammation
  • Mitochondria
  • NADPH oxidase
  • Nitric oxide
  • Oxidants
  • Poly(ADP-ribose) polymerase
  • Poly(ADP-ribose) synthetase
  • Pyridine nucleotides
  • Reperfusion
  • Shock
  • Superoxide

ASJC Scopus subject areas

  • Physiology

Cite this

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title = "Pathophysiological aspects of cellular pyridine nucleotide metabolism: Focus on the vascular endothelium. Review",
abstract = "In recent years, pyridine nucleotides NAD(H) and NADP(H) have been established as an important molecules in physiological and pathophysiological signaling and cell injury pathways. Protein modification is catalyzed by ADP-ribosyl transferases that attach the ADP-ribose moiety of NAD+ to specific aminoacid residues of the acceptor proteins, with significant changes in the function of these acceptors. Mono(ADP-ribosyl)ation reactions have been implicated to play a role both in physiological responses and in cellular responses to bacterial toxins. Cyclic ADP-ribose formation also utilizes NAD+ and primarily serves as physiological, signal transduction mechanisms regulating intracellular calcium homeostasis. In pathophysiological conditions associated with oxidative stress (such as various forms of inflammation and reperfusion injury), activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) occurs, with subsequent, substantial fall in cellular NAD+ and ATP levels, which can determine the viability and function of the affected cells. In addition, NADPH oxidases can significantly affect the balance and fate of NAD+ and NADP in oxidatively stressed cells and can facilitate the generation of various positive feedback cycles of injury. Under severe oxidant conditions, direct oxidative damage to NAD + has also been reported. The current review focuses on PARP and on NADPH oxidases, as pathophysiologically relevant factors in creating disturbances in the cellular pyridine nucleotide balance. A separate section describes how these mechanisms apply to the pathogenesis of endothelial cell injury in selected cardiovascular pathophysiological conditions.",
keywords = "DNA, Endothelium, Free radicals, Inflammation, Mitochondria, NADPH oxidase, Nitric oxide, Oxidants, Poly(ADP-ribose) polymerase, Poly(ADP-ribose) synthetase, Pyridine nucleotides, Reperfusion, Shock, Superoxide",
author = "Csaba Szabo",
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AU - Szabo, Csaba

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AB - In recent years, pyridine nucleotides NAD(H) and NADP(H) have been established as an important molecules in physiological and pathophysiological signaling and cell injury pathways. Protein modification is catalyzed by ADP-ribosyl transferases that attach the ADP-ribose moiety of NAD+ to specific aminoacid residues of the acceptor proteins, with significant changes in the function of these acceptors. Mono(ADP-ribosyl)ation reactions have been implicated to play a role both in physiological responses and in cellular responses to bacterial toxins. Cyclic ADP-ribose formation also utilizes NAD+ and primarily serves as physiological, signal transduction mechanisms regulating intracellular calcium homeostasis. In pathophysiological conditions associated with oxidative stress (such as various forms of inflammation and reperfusion injury), activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) occurs, with subsequent, substantial fall in cellular NAD+ and ATP levels, which can determine the viability and function of the affected cells. In addition, NADPH oxidases can significantly affect the balance and fate of NAD+ and NADP in oxidatively stressed cells and can facilitate the generation of various positive feedback cycles of injury. Under severe oxidant conditions, direct oxidative damage to NAD + has also been reported. The current review focuses on PARP and on NADPH oxidases, as pathophysiologically relevant factors in creating disturbances in the cellular pyridine nucleotide balance. A separate section describes how these mechanisms apply to the pathogenesis of endothelial cell injury in selected cardiovascular pathophysiological conditions.

KW - DNA

KW - Endothelium

KW - Free radicals

KW - Inflammation

KW - Mitochondria

KW - NADPH oxidase

KW - Nitric oxide

KW - Oxidants

KW - Poly(ADP-ribose) polymerase

KW - Poly(ADP-ribose) synthetase

KW - Pyridine nucleotides

KW - Reperfusion

KW - Shock

KW - Superoxide

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EP - 193

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JF - Physiology International

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