Increased poly(ADP-ribosyl)ation in skeletal muscle tissue of pediatric patients with severe burn injury

Prevention by propranolol treatment

Gábor Oláh, Celeste Finnerty, Elena Sbrana, Itoro Elijah, Domokos Gerö, David Herndon, Csaba Szabo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) has been shown to promote cellular energetic collapse and cellular necrosis in various forms of critical illness. Most of the evidence implicating the PARP pathway in disease processes is derived from preclinical studies. With respect to PARP and burns, studies in rodent and large animal models of burn injury have demonstrated the activation of PARP in various tissues and the beneficial effect of its pharmacological inhibition. The aims of the current study were to measure the activation of PARP in human skeletal muscle biopsies at various stages of severe pediatric burn injury and to identify the cell types where this activation may occur. Another aim of the study was to test the effect of propranolol (an effective treatment of patients with burns) on the activation of PARP in skeletal muscle biopsies. Poly(ADP-ribose) polymerase activation was measured by Western blotting for its product, poly(ADP-ribose) (PAR). The localization of PARP activation was determined by PAR immunohistochemistry. The results showed that PARP becomes activated in the skeletal muscle tissue after burns, with the peak of the activation occurring in the middle stage of the disease (13-18 days after burns). Even at the late stage of the disease (69-369 days after burn), an elevated degree of PARP activation persisted in some of the patients. Immunohistochemical studies localized the staining of PAR primarily to vascular endothelial cells and occasionally to resident mononuclear cells. There was a marked suppression of PARP activation in the skeletal muscle biopsies of patients who received propranolol treatment. We conclude that human burn injury is associated with the activation of PARP. We hypothesize that this response may contribute to the inflammatory responses and cell dysfunction in burns. Some of the clinical benefit of propranolol in burns may be related to its inhibitory effect on PARP activation.

Original languageEnglish (US)
Pages (from-to)18-23
Number of pages6
JournalShock
Volume36
Issue number1
DOIs
StatePublished - Jul 2011

Fingerprint

Poly(ADP-ribose) Polymerases
Propranolol
Adenosine Diphosphate
Skeletal Muscle
Pediatrics
Muscles
Wounds and Injuries
Burns
Therapeutics
Biopsy
Poly Adenosine Diphosphate Ribose
Enzyme Activation
Critical Illness
Rodentia
Necrosis
Endothelial Cells
Animal Models

Keywords

  • burns
  • contraction
  • endothelial cell
  • inflammation
  • Nitric oxide
  • peroxynitrite
  • poly(ADP-ribose) polymerase
  • superoxide
  • vascular

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Increased poly(ADP-ribosyl)ation in skeletal muscle tissue of pediatric patients with severe burn injury : Prevention by propranolol treatment. / Oláh, Gábor; Finnerty, Celeste; Sbrana, Elena; Elijah, Itoro; Gerö, Domokos; Herndon, David; Szabo, Csaba.

In: Shock, Vol. 36, No. 1, 07.2011, p. 18-23.

Research output: Contribution to journalArticle

Oláh, Gábor ; Finnerty, Celeste ; Sbrana, Elena ; Elijah, Itoro ; Gerö, Domokos ; Herndon, David ; Szabo, Csaba. / Increased poly(ADP-ribosyl)ation in skeletal muscle tissue of pediatric patients with severe burn injury : Prevention by propranolol treatment. In: Shock. 2011 ; Vol. 36, No. 1. pp. 18-23.
@article{d3ae0d6c4e1f47e8b62d27149d97b23b,
title = "Increased poly(ADP-ribosyl)ation in skeletal muscle tissue of pediatric patients with severe burn injury: Prevention by propranolol treatment",
abstract = "Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) has been shown to promote cellular energetic collapse and cellular necrosis in various forms of critical illness. Most of the evidence implicating the PARP pathway in disease processes is derived from preclinical studies. With respect to PARP and burns, studies in rodent and large animal models of burn injury have demonstrated the activation of PARP in various tissues and the beneficial effect of its pharmacological inhibition. The aims of the current study were to measure the activation of PARP in human skeletal muscle biopsies at various stages of severe pediatric burn injury and to identify the cell types where this activation may occur. Another aim of the study was to test the effect of propranolol (an effective treatment of patients with burns) on the activation of PARP in skeletal muscle biopsies. Poly(ADP-ribose) polymerase activation was measured by Western blotting for its product, poly(ADP-ribose) (PAR). The localization of PARP activation was determined by PAR immunohistochemistry. The results showed that PARP becomes activated in the skeletal muscle tissue after burns, with the peak of the activation occurring in the middle stage of the disease (13-18 days after burns). Even at the late stage of the disease (69-369 days after burn), an elevated degree of PARP activation persisted in some of the patients. Immunohistochemical studies localized the staining of PAR primarily to vascular endothelial cells and occasionally to resident mononuclear cells. There was a marked suppression of PARP activation in the skeletal muscle biopsies of patients who received propranolol treatment. We conclude that human burn injury is associated with the activation of PARP. We hypothesize that this response may contribute to the inflammatory responses and cell dysfunction in burns. Some of the clinical benefit of propranolol in burns may be related to its inhibitory effect on PARP activation.",
keywords = "burns, contraction, endothelial cell, inflammation, Nitric oxide, peroxynitrite, poly(ADP-ribose) polymerase, superoxide, vascular",
author = "G{\'a}bor Ol{\'a}h and Celeste Finnerty and Elena Sbrana and Itoro Elijah and Domokos Ger{\"o} and David Herndon and Csaba Szabo",
year = "2011",
month = "7",
doi = "10.1097/SHK.0b013e3182168d8f",
language = "English (US)",
volume = "36",
pages = "18--23",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Increased poly(ADP-ribosyl)ation in skeletal muscle tissue of pediatric patients with severe burn injury

T2 - Prevention by propranolol treatment

AU - Oláh, Gábor

AU - Finnerty, Celeste

AU - Sbrana, Elena

AU - Elijah, Itoro

AU - Gerö, Domokos

AU - Herndon, David

AU - Szabo, Csaba

PY - 2011/7

Y1 - 2011/7

N2 - Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) has been shown to promote cellular energetic collapse and cellular necrosis in various forms of critical illness. Most of the evidence implicating the PARP pathway in disease processes is derived from preclinical studies. With respect to PARP and burns, studies in rodent and large animal models of burn injury have demonstrated the activation of PARP in various tissues and the beneficial effect of its pharmacological inhibition. The aims of the current study were to measure the activation of PARP in human skeletal muscle biopsies at various stages of severe pediatric burn injury and to identify the cell types where this activation may occur. Another aim of the study was to test the effect of propranolol (an effective treatment of patients with burns) on the activation of PARP in skeletal muscle biopsies. Poly(ADP-ribose) polymerase activation was measured by Western blotting for its product, poly(ADP-ribose) (PAR). The localization of PARP activation was determined by PAR immunohistochemistry. The results showed that PARP becomes activated in the skeletal muscle tissue after burns, with the peak of the activation occurring in the middle stage of the disease (13-18 days after burns). Even at the late stage of the disease (69-369 days after burn), an elevated degree of PARP activation persisted in some of the patients. Immunohistochemical studies localized the staining of PAR primarily to vascular endothelial cells and occasionally to resident mononuclear cells. There was a marked suppression of PARP activation in the skeletal muscle biopsies of patients who received propranolol treatment. We conclude that human burn injury is associated with the activation of PARP. We hypothesize that this response may contribute to the inflammatory responses and cell dysfunction in burns. Some of the clinical benefit of propranolol in burns may be related to its inhibitory effect on PARP activation.

AB - Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) has been shown to promote cellular energetic collapse and cellular necrosis in various forms of critical illness. Most of the evidence implicating the PARP pathway in disease processes is derived from preclinical studies. With respect to PARP and burns, studies in rodent and large animal models of burn injury have demonstrated the activation of PARP in various tissues and the beneficial effect of its pharmacological inhibition. The aims of the current study were to measure the activation of PARP in human skeletal muscle biopsies at various stages of severe pediatric burn injury and to identify the cell types where this activation may occur. Another aim of the study was to test the effect of propranolol (an effective treatment of patients with burns) on the activation of PARP in skeletal muscle biopsies. Poly(ADP-ribose) polymerase activation was measured by Western blotting for its product, poly(ADP-ribose) (PAR). The localization of PARP activation was determined by PAR immunohistochemistry. The results showed that PARP becomes activated in the skeletal muscle tissue after burns, with the peak of the activation occurring in the middle stage of the disease (13-18 days after burns). Even at the late stage of the disease (69-369 days after burn), an elevated degree of PARP activation persisted in some of the patients. Immunohistochemical studies localized the staining of PAR primarily to vascular endothelial cells and occasionally to resident mononuclear cells. There was a marked suppression of PARP activation in the skeletal muscle biopsies of patients who received propranolol treatment. We conclude that human burn injury is associated with the activation of PARP. We hypothesize that this response may contribute to the inflammatory responses and cell dysfunction in burns. Some of the clinical benefit of propranolol in burns may be related to its inhibitory effect on PARP activation.

KW - burns

KW - contraction

KW - endothelial cell

KW - inflammation

KW - Nitric oxide

KW - peroxynitrite

KW - poly(ADP-ribose) polymerase

KW - superoxide

KW - vascular

UR - http://www.scopus.com/inward/record.url?scp=79959688116&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959688116&partnerID=8YFLogxK

U2 - 10.1097/SHK.0b013e3182168d8f

DO - 10.1097/SHK.0b013e3182168d8f

M3 - Article

VL - 36

SP - 18

EP - 23

JO - Shock

JF - Shock

SN - 1073-2322

IS - 1

ER -