Alterations of the thioredoxin system during subarachnoid hemorrhage-induced cerebral vasospasm

Kaya, Bülent; Erdi, Fatih; Kılınç, İbrahim; Keskin, Fatıh; Feyzioğlu, Bahadır; Esen, Hasan; Karataş, Yaşar; Uyar, Mehmet; Kalkan, Erdal

doi:10.1007/s00701-015-2390-z

Cited by 13 publications

(10 citation statements)

References 19 publications

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“…Several studies recently reported that TXNIP plays dual pro-inflammatory and pro-apoptotic roles in ischaemic diseases [23, 39], but the relationship between TXNIP and SAH has not been elucidated. Kaya and colleagues reported that SAH induced TXNIP mRNA expression [40]. Therefore, we speculated that TXNIP may also participate in the pathogenesis of EBI.…”

Section: Discussionmentioning

confidence: 91%

Thioredoxin-interacting protein links endoplasmic reticulum stress to inflammatory brain injury and apoptosis after subarachnoid haemorrhage

Zhao

Che

Zhang

et al. 2017

J Neuroinflammation

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BackgroundEarly brain injury (EBI) is considered a major contributor to the high morbidity and mortality associated with subarachnoid haemorrhage (SAH). Both of sterile inflammation and apoptosis are considered the important causes of EBI. Recently, it was confirmed that thioredoxin-interacting protein (TXNIP) not only participates in inflammatory amplification but also stimulates the apoptosis signalling cascade pathway. However, whether the effects of TXNIP influence the pathogenesis of SAH remains unclear. Here, we hypothesize that TXNIP activity induced by endoplasmic reticulum stress (ER stress) may contribute to the pathogenesis of EBI through pro-inflammatory and pro-apoptotic mechanisms.MethodsA total of 299 male Sprague–Dawley rats were used to create SAH models. Resveratrol (RES, 60 mg/kg) and two TXNIP small interfering RNA (siRNA) were used to inhibit TXNIP expression. The specific inhibitors of ER stress sensors were used to disrupt the link between TXNIP and ER stress. SAH grade, neurological deficits, brain water content and blood–brain barrier (BBB) permeability were evaluated simultaneously as prognostic indicators. Fluorescent double-labelling was employed to detect the location of TXNIP in cerebral cells. Western blot and TUNEL were performed to study the mechanisms of TXNIP and EBI.ResultsWe found that TXNIP expression significantly increased after SAH, peaking at 48 h (0.48 ± 0.04, up to 3.2-fold) and decreasing at 72 h after surgery. This process was accompanied by the generation of inflammation-associated factors. TXNIP was expressed in the cytoplasm of neurons and was widely co-localized with TUNEL-positive cells in both the hippocampus and the cortex of SAH rats. We discovered for the first time that TXNIP was co-localized in neural immunocytes (microglia and astrocytes). After administration of RES, TXNIP siRNA and ER stress inhibitors, TXNIP expression was significantly reduced and the crosstalk between TXNIP and ER stress was disrupted; this was accompanied by a reduction in inflammatory and apoptotic factors, as well as attenuation of the prognostic indices.ConclusionsThese results may represent the critical evidence to support the pro-inflammatory and pro-apoptotic effects of TXNIP after SAH. Our data suggest that TXNIP participates in EBI after SAH by mediating inflammation and apoptosis; these pathways may represent a potential therapeutic strategy for SAH treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0878-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 91%

Thioredoxin-interacting protein links endoplasmic reticulum stress to inflammatory brain injury and apoptosis after subarachnoid haemorrhage

Zhao

Che

Zhang

et al. 2017

J Neuroinflammation

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“…Nonenzymatic antioxidants are an important class of antioxidants that play important roles in the pathogenesis of cerebral hemorrhage. These include glutathione [ 53 , 109 ], antioxidant vitamins [ 106 , 110 ], uric acid [ 111 ], ubiquinone-reducing substances [ 54 , 112 ], metallothionein [ 113 ], and thioredoxin system [ 114 , 115 ]. However, methods for the detection of oxidative stress related nonenzymatic antioxidants in the peripheral blood are few; one study on the level of glutathione (GSH) in umbilical cord blood after neonatal periventricular hemorrhage found that cord blood GSH level was not related to intraventricular hemorrhage in low-birthweight neonates [ 116 ].…”

Section: Detection Of the Level Of Oxidative Stressmentioning

confidence: 99%

“…Studies have found that TOS and NO serum levels in patients are significantly increased after cerebral hemorrhage, while TAC levels and catalase activity are significantly reduced. Therefore, the oxidative stress index (OSI) is increased [ 115 , 127 ].…”

Section: Detection Of the Level Of Oxidative Stressmentioning

confidence: 99%

Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

Duan

Wen

Shen

et al. 2016

Oxidative Medicine and Cellular Longevity

231

177

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Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.

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“…According to several reports, increased mRNA expression of TXNIP has been also detected in brains affected with sub-arachnoid hemorrhage (SAH) [130, 131]. In a rabbit model of SAH, the brain stem levels of TRX1 and TRX reductase (TRXR) decreased in parallel with a rise in the expression of TXNIP [130].…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin-Interacting Protein (TXNIP) in Cerebrovascular and Neurodegenerative Diseases: Regulation and Implication

2018

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Neurological diseases, including acute attacks (e.g., ischemic stroke) and chronic neurodegenerative diseases (e.g., Alzheimer's disease), have always been one of the leading cause of morbidity and mortality worldwide. These debilitating diseases represent an enormous disease burden, not only in terms of health suffering but also in economic costs. Although the clinical presentations differ for these diseases, a growing body of evidence suggests that oxidative stress and inflammatory responses in brain tissue significantly contribute to their pathology. However, therapies attempting to prevent oxidative damage or inhibiting inflammation have shown little success. Identification and targeting endogenous "upstream" mediators that normalize such processes will lead to improve therapeutic strategy of these diseases. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of the thioredoxin (TRX) system, a major cellular thiol-reducing and antioxidant system. TXNIP regulating redox/glucose-induced stress and inflammation, now is known to get upregulated in stroke and other brain diseases, and represents a promising therapeutic target. In particular, there is growing evidence that glucose strongly induces TXNIP in multiple cell types, suggesting possible physiological roles of TXNIP in glucose metabolism. Recently, a significant body of literature has supported an essential role of TXNIP in the activation of the NOD-like receptor protein (NLRP3)-inflammasome, a well-established multi-molecular protein complex and a pivotal mediator of sterile inflammation. Accordingly, TXNIP has been postulated to reside centrally in detecting cellular damage and mediating inflammatory responses to tissue injury. The majority of recent studies have shown that pharmacological inhibition or genetic deletion of TXNIP is neuroprotective and able to reduce detrimental aspects of pathology following cerebrovascular and neurodegenerative diseases. Conspicuously, the mainstream of the emerging evidences is highlighting TXNIP link to damaging signals in endothelial cells. Thereby, here, we keep the trend to present the accumulative data on CNS diseases dealing with vascular integrity. This review aims to summarize evidence supporting the significant contribution of regulatory mechanisms of TXNIP with the development of brain diseases, explore pharmacological strategies of targeting TXNIP, and outline obstacles to be considered for efficient clinical translation.

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Alterations of the thioredoxin system during subarachnoid hemorrhage-induced cerebral vasospasm

Abstract: The Trx system seems to be negatively affected by the simultaneously interrelated enzymatic alterations during cerebral vasospasm.

Cited by 13 publications

References 19 publications

Thioredoxin-interacting protein links endoplasmic reticulum stress to inflammatory brain injury and apoptosis after subarachnoid haemorrhage

Thioredoxin-interacting protein links endoplasmic reticulum stress to inflammatory brain injury and apoptosis after subarachnoid haemorrhage

Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

Thioredoxin-Interacting Protein (TXNIP) in Cerebrovascular and Neurodegenerative Diseases: Regulation and Implication

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