Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection

Rainer Schulz, Philipp Maximilian Görge, A. Görbe, P. Ferdinándy, Paul D. Lampe, Luc Leybaert

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Abstract Connexins are widely distributed proteins in the body that are crucially important for heart and brain functions. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localization at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in the mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodeling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injuries as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissues following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection.

Original languageEnglish
Article number6791
Pages (from-to)90-106
Number of pages17
JournalPharmacology and Therapeutics
Volume153
DOIs
Publication statusPublished - Aug 4 2015

Fingerprint

Connexin 43
Connexins
Reperfusion Injury
Gap Junctions
Therapeutics
Ischemia
Phosphorylation
Heart Injuries
Sarcolemma
Brain
Hypercholesterolemia
Brain Ischemia
Cardiac Myocytes
Brain Injuries
Hypertrophy
Reperfusion
Neuroprotection
Mitochondria
Respiration
Heart Failure

Keywords

  • Brain
  • Cardioprotection
  • Connexin 43
  • Heart
  • Mitochondria
  • Neuroprotection

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection. / Schulz, Rainer; Görge, Philipp Maximilian; Görbe, A.; Ferdinándy, P.; Lampe, Paul D.; Leybaert, Luc.

In: Pharmacology and Therapeutics, Vol. 153, 6791, 04.08.2015, p. 90-106.

Research output: Contribution to journalArticle

Schulz, Rainer ; Görge, Philipp Maximilian ; Görbe, A. ; Ferdinándy, P. ; Lampe, Paul D. ; Leybaert, Luc. / Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection. In: Pharmacology and Therapeutics. 2015 ; Vol. 153. pp. 90-106.
@article{e55c98e6159240edb57f908273dbadbc,
title = "Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection",
abstract = "Abstract Connexins are widely distributed proteins in the body that are crucially important for heart and brain functions. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localization at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in the mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodeling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injuries as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissues following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection.",
keywords = "Brain, Cardioprotection, Connexin 43, Heart, Mitochondria, Neuroprotection",
author = "Rainer Schulz and G{\"o}rge, {Philipp Maximilian} and A. G{\"o}rbe and P. Ferdin{\'a}ndy and Lampe, {Paul D.} and Luc Leybaert",
year = "2015",
month = "8",
day = "4",
doi = "10.1016/j.pharmthera.2015.06.005",
language = "English",
volume = "153",
pages = "90--106",
journal = "Pharmacology and Therapeutics",
issn = "0163-7258",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection

AU - Schulz, Rainer

AU - Görge, Philipp Maximilian

AU - Görbe, A.

AU - Ferdinándy, P.

AU - Lampe, Paul D.

AU - Leybaert, Luc

PY - 2015/8/4

Y1 - 2015/8/4

N2 - Abstract Connexins are widely distributed proteins in the body that are crucially important for heart and brain functions. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localization at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in the mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodeling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injuries as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissues following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection.

AB - Abstract Connexins are widely distributed proteins in the body that are crucially important for heart and brain functions. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localization at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in the mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodeling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injuries as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissues following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection.

KW - Brain

KW - Cardioprotection

KW - Connexin 43

KW - Heart

KW - Mitochondria

KW - Neuroprotection

UR - http://www.scopus.com/inward/record.url?scp=84938423002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938423002&partnerID=8YFLogxK

U2 - 10.1016/j.pharmthera.2015.06.005

DO - 10.1016/j.pharmthera.2015.06.005

M3 - Article

C2 - 26073311

AN - SCOPUS:84938423002

VL - 153

SP - 90

EP - 106

JO - Pharmacology and Therapeutics

JF - Pharmacology and Therapeutics

SN - 0163-7258

M1 - 6791

ER -