ClC-3 deficiency protects preadipocytes against apoptosis induced by palmitate in vitro and in type 2 diabetes mice

Huang, Yunying; Huang, Xiong-Qin; Zhao, Liyan; Sun, Fangyun; Chen, Wenliang; Du, Junbao; Yuan, Feng; Li, Jie; Huang, Xuelian; Liu, Jie; Lv, Xiao‐Fei; Guan, Yong‐Yuan; Chen, Jianwen; Wang, Guan-Lei

doi:10.1007/s10495-014-1021-0

Cited by 17 publications

(23 citation statements)

References 51 publications

(79 reference statements)

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“…A high level of ClC-3 alone is sufficient to cause Nox-derived ROS production. It has been shown that ClC-3 expression is upregulated in various cardiovascular diseases featured by increased oxidative stress, including hypertension [29], atherosclerosis [8], and diabetes [30]. Consistently, our present study also showed an increase in ClC-3 expression in Ang II-treated endothelial cells.…”

Section: Discussionsupporting

confidence: 91%

ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation

et al. 2018

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Recent evidence suggests that ClC-3, a member of the ClC family of Cl channels or Cl/H antiporters, plays a critical role in NADPH oxidase-derived reactive oxygen species (ROS) generation. However, the underling mechanisms remain unclear. In this study we investigated the effects and mechanisms of ClC-3 on NADPH oxidase activation and ROS generation in endothelial cells. Treatment with angiotensin II (Ang II, 1 μmol/L) significantly elevated ClC-3 expression in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, Ang II treatment increased ROS production and NADPH oxidase activity, an effect that could be significantly inhibited by knockdown of ClC-3, and further enhanced by overexpression of ClC-3. SA-β-galactosidase staining showed that ClC-3 silencing abolished Ang II-induced HUVEC senescence, whereas ClC-3 overexpression caused the opposite effects. We further showed that Ang II treatment increased the translocation of p47phox and p67phox from the cytosol to membrane, accompanied by elevated Nox2 and p22phox expression, which was significantly attenuated by knockdown of ClC-3 and potentiated by overexpression of ClC-3. Moreover, overexpression of ClC-3 increased Ang II-induced phosphorylation of p47phox and p38 MAPK in HUVECs. Pretreatment with a p38 inhibitor SB203580 abolished ClC-3 overexpression-induced increase in p47phox phosphorylation, as well as NADPH oxidase activity and ROS generation. Our results demonstrate that ClC-3 acts as a positive regulator of Ang II-induced NADPH oxidase activation and ROS production in endothelial cells, possibly via promoting both Nox2/p22phox expression and p38 MAPK-dependent p47phox/p67phox membrane translocation, then increasing Nox2 NADPH oxidase complex formation.

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Section: Discussionsupporting

confidence: 91%

ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation

et al. 2018

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“…As shown in table 4, the Xyl-B treatment significantly improved the neurological outcome of the tMCAO mice compared with that of the vehicle group (P<0.05 vs Vehicle controls, n=7 mice/group). Consistently, the tMCAO mice that were treated with edaravone also displayed significant neuroprotective effects compared with the vehicle control Xyl-B decreased the ROS level and increased the SOD2 level Reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO), play a key role in the pathophysiological response of the brain after an ischemia injury [20] . Here, we detected the total ROS levels by DHE staining.…”

Section: Xyl-b Improved the Neurological Outcomementioning

confidence: 74%

“…Quantitative real-time PCR The quantitative real-time PCR experiment was conducted as described previously [20] . Briefly, the total RNA from the ischemic region was isolated using the TRIzol reagent (Invitrogen).…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Xyloketal B alleviates cerebral infarction and neurologic deficits in a mouse stroke model by suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway

Pan

et al. 2017

Acta Pharmacol Sin

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Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus Xylaria sp. We previously demonstrated that pretreatment with Xyl-B exerted neuroprotective effects and attenuated hypoxic-ischemic brain injury in neonatal mice. In the present study we investigated the neuroprotective effects of pre- and post-treatment with Xyl-B in adult mice using a transient middle cerebral artery occlusion (tMCAO) model, and explored the underlying mechanisms. Adult male C57 mice were subjected to tMCAO surgery. For the pre-treatment, Xyl-B was given via multiple injections (12.5, 25, and 50 mg·kg·d, ip) 48 h, 24 h and 30 min before ischemia. For the post-treatment, a single dose of Xyl-B (50 mg/kg, ip) was injected at 0, 1 or 2 h after the onset of ischemia. The regional cerebral perfusion was monitored using a laser-Doppler flowmeter. TTC staining was performed to determine the brain infarction volume. We found that both pre-treatment with Xyl-B (50 mg/kg) and post-treatment with Xyl-B (50 mg/kg) significantly reduced the infarct volume, but had no significant hemodynamic effects. Treatment with Xyl-B also significantly alleviated the neurological deficits in tMCAO mice. Furthermore, treatment with Xyl-B significantly attenuated ROS overproduction in brain tissues; increased the MnSOD protein levels, suppressed TLR4, NF-κB and iNOS protein levels; and downregulated the mRNA levels of proinflammatory cytokines, including IL-1β, TNF-α, IL-6 and IFN-γ. Moreover, Xyl-B also protected blood-brain barrier integrity in tMCAO mice. In conclusion, Xyl-B administered within 2 h after the onset of stroke effectively protects against focal cerebral ischemia; the underlying mechanism may be related to suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway.

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“…Previous studies have demonstrated that ROS plays a key role in the pathophysiological response of the brain after I/R injury [32] . The results showed that I/R injury significantly increased ROS production compared to the normal rats.…”

Section: X1s Reduces the Level Of Reactive Oxygen Species (Ros) In Imentioning

confidence: 99%

Xueshuantong injection (lyophilized) combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress

Wang

Chai

et al. 2017

Acta Pharmacol Sin

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Salvianolate lyophilized injection (SLI) and Xueshuantong injection (lyophilized) (XST) are two herbal standardized preparations that have been widely used in China for the treatment of acute cerebral infarction. In this study, we investigated the neuroprotective effects of SLI combined with XST in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Wistar rats were subjected to 1.5 h of MCAO followed by reperfusion for 3 h, then were treated with SLI or XST alone, or with their combinations via tail vein injection daily for 3 d. Edaravone (EDI, 6 mg·kg·d) was used as a positive control drug, We showed that administration of a combination of 1X1S (XST 100 mg·kg·d plus SLI 21 mg·kg·d) more effectively protected the ischemic brains than SLI or XST used alone. Administration of 1X1S not only significantly decreased neurological deficit scores and infarct volumes and increased regional cerebral blood flow, but also inhibited the activation of both microglia and astrocytes in the hippocampus. Furthermore, administration of 1X1S significantly decreased the levels of MDA and ROS with concomitant increases in the levels of antioxidant activity (SOD, CAT and GSH) in the brain tissues as compared with SLI and XST used alone. Moreover, administration of 1X1S remarkably upregulated the expression of Nrf-2, HO-1 and NQO-1, and downregulated the expression of Keap1 and facilitated the nuclear translocation of Nrf-2 in the brain tissues as compared with XST used alone. Our study demonstrates that a combination of 1X1S effectively protects MCAO/R injury via suppressing oxidative stress and the Nrf-2/Keap1 pathway.

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ClC-3 deficiency protects preadipocytes against apoptosis induced by palmitate in vitro and in type 2 diabetes mice

Cited by 17 publications

References 51 publications

ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation

ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation

Xyloketal B alleviates cerebral infarction and neurologic deficits in a mouse stroke model by suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway

Xueshuantong injection (lyophilized) combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress

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