Connexin 43 and Its Hemichannels Mediate Hypoxia–Ischemia-Induced Cell Death in Neonatal Rats

Wang, Jingwei; Ma, Aihua; Xi, Jiashui; Wang, Yulin; Zhao, Bojun

doi:10.1177/2329048x14544955

Cited by 9 publications

(10 citation statements)

References 40 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An upregulation of Cx43 has been shown to occur in adult and perinatal animals after HI and in adult human post-mortem studies of cerebral ischemia (Nakase et al, 2006, 2009; Davidson et al, 2012; Wang et al, 2014; Li et al, 2015). The timing of this Cx43 increase varies between studies, with Cx43 mRNA levels significantly increased at 6 h after carotid artery occlusion in near-term fetal sheep (Davidson et al, 2012).…”

Section: Connexin Hemichannelsmentioning

confidence: 99%

“…Protein levels progressively increased in the ischemic region from 8 h to 7 days after common carotid artery ligation and hypoxia (commonly referred to as Rice-Vannucci model of HI) in post-natal day (P)7 rats (equivalent to 33–34 weeks of human brain maturation) (Li et al, 2015). In the subventricular zone, however, Wang and colleagues reported Cx43 protein expression was only significantly increased from 24 h after the same insult in P7 rats (Wang et al, 2014). However, there was no change in hippocampal Cx43 protein expression at all time-points between 10 min and 35 days after acute hypoxia in P10 rats (equivalent to human term brain maturation) (Zeinieh et al, 2010).…”

Section: Connexin Hemichannelsmentioning

confidence: 99%

“…The mechanisms behind this spread are not well-understood. Increasing evidence supports the opening of cell membrane channels after HI as one of the mediators of this propagation of injury, particularly connexin hemichannels, which are the unopposed half of a gap junction, forming large conductance channels in the cell membrane (Davidson et al, 2012, 2014; Wang et al, 2014; Li et al, 2015). Pannexin channels may also open under pathological conditions, although they appear to be tightly regulated (Qiu and Dahl, 2009) and their role in the developing brain remains unclear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Connexin and Pannexin Channels in Perinatal Brain Injury and Inflammation

et al. 2019

View full text Add to dashboard Cite

Perinatal brain injury remains a major cause of death and life-long disability. Perinatal brain injury is typically associated with hypoxia-ischemia and/or infection/inflammation. Both hypoxia-ischemia and infection trigger an inflammatory response in the brain. The inflammatory response can contribute to brain cell loss and chronic neuroinflammation leading to neurological impairments. It is now well-established that brain injury evolves over time, and shows a striking spread from injured to previously uninjured regions of the brain. There is increasing evidence that this spread is related to opening of connexin hemichannels and pannexin channels, both of which are large conductance membrane channels found in almost all cell types in the brain. Blocking connexin hemichannels within the first 3 h after hypoxia-ischemia has been shown to improve outcomes in term equivalent fetal sheep but it is important to also understand the downstream pathways linking membrane channel opening with the development of injury in order to identify new therapeutic targets. Open membrane channels release adenosine triphosphate (ATP), and other neuroactive molecules, into the extracellular space. ATP has an important physiological role, but has also been reported to act as a damage-associated molecular pattern (DAMP) signal mediated through specific purinergic receptors and so act as a primary signal 1 in the innate immune system inflammasome pathway. More crucially, extracellular ATP is a key inflammasome signal 2 activator, with purinergic receptor binding triggering the assembly of the multi-protein inflammasome complex. The inflammasome pathway and complex formation contribute to activation of inflammatory caspases, and the release of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-18, and vascular endothelial growth factor (VEGF). We propose that the NOD-like receptor protein-3 (NLRP3) inflammasome, which has been linked to inflammatory responses in models of ischemic stroke and various inflammatory diseases, may be one mechanism by which connexin hemichannel opening especially mediates perinatal brain injury.

show abstract

Section: Connexin Hemichannelsmentioning

confidence: 99%

Section: Connexin Hemichannelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Connexin and Pannexin Channels in Perinatal Brain Injury and Inflammation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…According to this hypothesis, it has been proposed HC activity inhibition has a protective effect against inflammation progression [ 43 , 173 , 174 , 175 , 176 , 177 ]. Since HCs are thought to mediate and enhance deleterious inflammatory effects, propagating signaling molecules and contributing to proinflammatory mediator release [ 120 , 178 , 179 , 180 ]. Different research groups are currently working on Cx–HCs modulators as potential therapeutic strategies, in addition to the currently approved treatments [ 181 ].…”

Section: Role Of Connexins In Inflammation During Drmentioning

confidence: 99%

An Update on Connexin Gap Junction and Hemichannels in Diabetic Retinopathy

González-Casanova

Schmachtenberg

Martı́nez

et al. 2021

IJMS

View full text Add to dashboard Cite

Diabetic retinopathy (DR) is one of the main causes of vision loss in the working age population. It is characterized by a progressive deterioration of the retinal microvasculature, caused by long-term metabolic alterations inherent to diabetes, leading to a progressive loss of retinal integrity and function. The mammalian retina presents an orderly layered structure that executes initial but complex visual processing and analysis. Gap junction channels (GJC) forming electrical synapses are present in each retinal layer and contribute to the communication between different cell types. In addition, connexin hemichannels (HCs) have emerged as relevant players that influence diverse physiological and pathological processes in the retina. This article highlights the impact of diabetic conditions on GJC and HCs physiology and their involvement in DR pathogenesis. Microvascular damage and concomitant loss of endothelial cells and pericytes are related to alterations in gap junction intercellular communication (GJIC) and decreased connexin 43 (Cx43) expression. On the other hand, it has been shown that the expression and activity of HCs are upregulated in DR, becoming a key element in the establishment of proinflammatory conditions that emerge during hyperglycemia. Hence, novel connexin HCs blockers or drugs to enhance GJIC are promising tools for the development of pharmacological interventions for diabetic retinopathy, and initial in vitro and in vivo studies have shown favorable results in this regard.

show abstract

“…Further experiments should be done to test this hypothesis. Some researchers suggest that upregulation of Cx43 expression can lead to astrocytic death and decrease cell viability, while downregulation of Cx43 expression can conduce to astrocytic survival [32].…”

Section: Discussionmentioning

confidence: 99%

Salidroside Attenuates Hypoxia-Induced Expression of Connexin 43 in Corpus Cavernosum Smooth Muscle Cells

Zhao

et al. 2020

Urol Int

View full text Add to dashboard Cite

Introduction: Connexin 43 (Cx43) is the major component of gap junction in corpus cavernosum smooth muscle, which allows rapid intercellular communication. Cx43 coordinates corpus cavernosum smooth muscle cells and ensures erectile function. The role of hypoxia in Cx43 dysfunction resulting in erectile dysfunction has not been well studied, and salidroside has shown cell protective effects under hypoxia. Objective: We aimed to investigate the protective role of salidroside and the underlying mechanisms in hypoxia-induced dysfunction of Cx43. Methods: Corpus cavernosum smooth muscle cells prepared from young male Sprague-Dawley rats were pretreated with or without salidroside and exposed to hypoxic condition for 48 h. The cell viability, expression of hypoxia-inducible factor-1α (HIF-1α) and Cx43, and Ca 2+ signals were investigated. Results: Pretreatment with salidroside attenuated loss of hypoxia-induced cell viability markedly and could downregulate the HIF-1α protein expression under hypoxia. Moreover, the expression of Cx43 was significantly increased by hypoxia but was decreased with salidroside pretreatment. The salidroside pretreated group exhibited enhanced release of intracellular Ca 2+ in corpus cavernosum smooth muscle cells compared with the hypoxia group after stimulation. Conclusion: Salidroside has a protective effect against hypoxia-induced damage to corpus cavernosum smooth muscle cells.

show abstract

Connexin 43 and Its Hemichannels Mediate Hypoxia–Ischemia-Induced Cell Death in Neonatal Rats

Cited by 9 publications

References 40 publications

The Role of Connexin and Pannexin Channels in Perinatal Brain Injury and Inflammation

The Role of Connexin and Pannexin Channels in Perinatal Brain Injury and Inflammation

An Update on Connexin Gap Junction and Hemichannels in Diabetic Retinopathy

Salidroside Attenuates Hypoxia-Induced Expression of Connexin 43 in Corpus Cavernosum Smooth Muscle Cells

Contact Info

Product

Resources

About