Tert-butylhydroquinone compromises survival in murine experimental stroke

Sun, Jiahong; Hu, Heng; Ren, Xuefang; Simpkins, James W.

doi:10.1016/j.ntt.2016.01.004

Cited by 13 publications

(9 citation statements)

References 27 publications

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“…If the cell density is below 8 × 10 3 cells per well, the basal OCR is too low to be analyzed (Figure 2 and Figure 3); if the cell density is above 32 × 10 3 cells per well, the cells do not respond to oligomycin or FCCP treatments (Figure 2 and Figure 3). The optimal cell density for this cell line in our experimental model is 16 × 10 3 cells per well, which demonstrates replicable results and sensitivity to stimuli 7 and treatments 10,14 . If a 24-well bioanalyzer is used, new titrations of the cell density would be required for the assay.…”

Section: Critical Steps Within the Protocolsupporting

confidence: 62%

“…We have demonstrated that insults to CVE cells following exposure to lipopolysaccharide (LPS) impair mitochondrial function in CVE cells and worsen stroke outcomes 7 . Tert-butylhydroquinone (tBHQ) increases stroke mortality by interfering with oxidative phosphorylation in CVE cells 10 . Therefore, the quantitative model of bioenergetic function in CVE cells not only pilots a series of mechanism-related studies for central nervous system (CNS) diseases, but also provides a breakthrough in drug screening of therapeutics targeting mitochondrial function in vascular biology.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells

Rellick

Simpkins

et al. 2016

JoVE

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The integrity of the blood-brain-barrier (BBB) is critical to prevent brain injury. Cerebral vascular endothelial (CVE) cells are one of the cell types that comprise the BBB; these cells have a very high-energy demand, which requires optimal mitochondrial function. In the case of disease or injury, the mitochondrial function in these cells can be altered, resulting in disease or the opening of the BBB. In this manuscript, we introduce a method to measure mitochondrial function in CVE cells by using whole, intact cells and a bioanalyzer. A mito-stress assay is used to challenge the cells that have been perturbed, either physically or chemically, and evaluate their bioenergetic function. Additionally, this method also provides a useful way to screen new therapeutics that have direct effects on mitochondrial function. We have optimized the cell density necessary to yield oxygen consumption rates that allow for the calculation of a variety of mitochondrial parameters, including ATP production, maximal respiration, and spare capacity. We also show the sensitivity of the assay by demonstrating that the introduction of the microRNA, miR-34a, leads to a pronounced and detectable decrease in mitochondrial activity. While the data shown in this paper is optimized for the bEnd.3 cell line, we have also optimized the protocol for primary CVE cells, further suggesting the utility in preclinical and clinical models. Video LinkThe video component of this article can be found at

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Section: Critical Steps Within the Protocolsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells

Rellick

Simpkins

et al. 2016

JoVE

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“…A recent study showed that Nrf2 upregulation by tBHQ significantly reduced the expression of cytoplasmic thioredoxin interacting protein, nod-like receptor protein 3 (NLRP3) inflammasome, and downstream factors caspase-1, IL-1β, and IL-18, all of which contribute to the Nrf2-mediated neuroprotection against ischemic outcomes after tMCAO (Hou et al, 2018 ). Interestingly, there is a contradictory report that tBHQ-exacerbated stroke damage (Sun et al, 2016 ), revealed by increased post-stroke mortality and worsened outcomes after pMCAO.…”

Section: Nrf2 Targeted Intervention In Ischemic Stroke—advancements Fmentioning

confidence: 99%

Critical Role of Nrf2 in Experimental Ischemic Stroke

2019

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Ischemic stroke is one of the leading causes of death and long-term disability worldwide; however, effective clinical approaches are still limited. The transcriptional factor Nrf2 is a master regulator in cellular and organismal defense against endogenous and exogenous stressors by coordinating basal and stress-inducible activation of multiple cytoprotective genes. The Nrf2 network not only tightly controls redox homeostasis but also regulates multiple intermediary metabolic processes. Therefore, targeting Nrf2 has emerged as an attractive therapeutic strategy for the prevention and treatment of CNS diseases including stroke. Here, the current understanding of the Nrf2 regulatory network is critically examined to present evidence for the contribution of Nrf2 pathway in rodent ischemic stroke models. This review outlines the literature for Nrf2 studies in preclinical stroke and focuses on the in vivo evidence for the role of Nrf2 in primary and secondary brain injuries. The dynamic change and functional importance of Nrf2 signaling, as well as Nrf2 targeted intervention, are revealed in permanent, transient, and global cerebral ischemia models. In addition, key considerations, pitfalls, and future potentials for Nrf2 studies in preclinical stroke investigation are discussed.

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“…Continuous tBHQ treatment markedly decreased and ameliorated proteinuria in type 1 diabetes mice [20]. Also, intra-cerebroventricular administration with tBHQ significantly reduced size of infraction and neurological disfunction was improved [21,22]. Moreover, tBHQ protected hepatocytes from saturated fatty acids induced cells death by enhancing autophagy [14].…”

Section: Discussionmentioning

confidence: 98%

Tert-butylhydroquinone mitigates Carbon Tetrachloride induced Hepatic Injury in mice

Zhang

et al. 2020

Int. J. Med. Sci.

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Tert-butylhydroquinone (tBHQ) is an antioxidant compound that exhibits cytoprotective effect in many tissues under pathological condition. However, its role in carbon tetrachloride (CCL4) induced liver injury is still unclear. Here we established a carbon tetrachloride induced hepatic injury model in mice to determine whether tBHQ can mitigate CCL4 induced liver damage. In our study, we found tBHQ exhibited protective effects in CCL4 treated mice model. TBHQ markedly improved hepatic function and decreased hepatic histopathological damage in vivo. In addition, tBHQ reduced levels of pro-inflammatory cytokines in mice model. Moreover, tBHQ mitigated apoptosis of hepatocytes, oxidative stress and lipid peroxidation in vivo and in vitro. We also found the possible mechanism of protective effects of tBHQ was associated with activation of Nrf2/ heme oxygenase-1 (HO-1) pathway. In conclusion, our study revealed tBHQ can be a potential therapeutic drug in treatment of acute hepatic injury.

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Tert-butylhydroquinone compromises survival in murine experimental stroke

Cited by 13 publications

References 27 publications

Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells

Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells

Critical Role of Nrf2 in Experimental Ischemic Stroke

Tert-butylhydroquinone mitigates Carbon Tetrachloride induced Hepatic Injury in mice

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