Neuronal KATP channels mediate hypoxic preconditioning and reduce subsequent neonatal hypoxic–ischemic brain injury

Sun, Hong‐Shuo; Xu, Baofeng; Chen, Wenliang; Xiao, Aiping; Turlova, Ekaterina; Alibraham, Ammar; Barszczyk, Andrew; Bae, Christine You-jin; Quan, Yi; Liu, Baosong; Lin, Pei; Sun, Chi; Deurloo, Marielle; Feng, Zhong‐Ping

doi:10.1016/j.expneurol.2014.10.003

Cited by 68 publications

(61 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our previous studies demonstrated that focal ischemia (transient middle cerebral artery [MCA] occlusion [tMCAO] model) in the brain led to larger cortical infarcts and more severe neurological deficits in adult Kir6.2 knockout mice (14). Our recent work showed that K ATP channels mediated hypoxic preconditioning-induced neuroprotection in a hypoxicischemic brain injury model in neonatal mice (15). Inhibition of K ATP channels by tolbutamide increased infarct volumes and opening of K ATP channels by diazoxidereduced infarct volumes (14,15).…”

mentioning

confidence: 99%

“…Our recent work showed that K ATP channels mediated hypoxic preconditioning-induced neuroprotection in a hypoxicischemic brain injury model in neonatal mice (15). Inhibition of K ATP channels by tolbutamide increased infarct volumes and opening of K ATP channels by diazoxidereduced infarct volumes (14,15). Opening of the K ATP channel hyperpolarizes the neurons and stabilizes the resting membrane potential during ischemia when energy failure reduces the ATP-to-ADP ratio (11,14,16).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cerebrovascular Safety of Sulfonylureas: The Role of KATP Channels in Neuroprotection and the Risk of Stroke in Patients With Type 2 Diabetes

Wang

et al. 2016

Diabetes

Self Cite

View full text Add to dashboard Cite

Sulfonylureas are ATP-sensitive potassium (K ATP ) channel blockers commonly used in the treatment of type 2 diabetes mellitus (T2DM). Activation of K ATP channels plays a neuroprotective role in ischemia; thus, whether sulfonylureas affect the outcomes of stroke in patients with T2DM needs to be further studied. In our study, streptozotocin (STZ)-induced diabetic mice subjected to transient middle cerebral artery occlusion (MCAO) showed larger areas of brain damage and poorer behavioral outcomes. Blocking the K ATP channel by tolbutamide increased neuronal injury induced by oxygen-glucose deprivation (OGD) in vitro and permanent MCAO (pMCAO) in vivo. Activating the K ATP channel by diazoxide reduced the effects of both the OGD and pMCAO. Western blot analysis in STZ mouse brains indicated an early increase in protein levels of N-methyl-D-aspartate receptor 2B and postsynaptic density protein-95, followed by a decrease in phosphorylation of glycogen synthase kinase 3b. Our systematic meta-analysis indicated that patients with T2DM treated with sulfonylureas had a higher odds ratio for stroke morbidity than those who received comparator drugs. Taken together, these results suggest that sulfonylurea treatment in patients with T2DM may inhibit the neuroprotective effects of K ATP channels and increase the risk of stroke.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Cerebrovascular Safety of Sulfonylureas: The Role of KATP Channels in Neuroprotection and the Risk of Stroke in Patients With Type 2 Diabetes

Wang

et al. 2016

Diabetes

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous experimental studies have utilized neonatal HI injury in rodent models to mimic the disease [19,20]. The model consists of a unilateral ligation of the common carotid artery followed by a period of hypoxia that leads to decreased blood flow and neuronal death in the ipsilateral hemisphere of the brain.…”

Section: Neuroprotective Effect Of Xyloketal B In Neonatal Hypoxic Ismentioning

confidence: 99%

Effects of marine compound xyloketal B on neuroprotection and potential drug development

2015

J Coast Life Med

View full text Add to dashboard Cite

“…This implies that DZ administration should result in the modulation of mitochondrial functions, ensuing from mK ATP channel opening and affect mitochondrial bioenergetics as it was shown in the heart, brain, liver, and pancreatic beta-cells [8][9][10]. But while the opening of mK ATP channel is generally thought to be cytoprotective, appraisal of bioenergetic and functional effects of mK ATP channel opening in mitochondria using DZ as pharmacological tool, is complicated by several side effects of this drug [2,11].…”

Section: Introductionmentioning

confidence: 99%

Direct and Off-Target Effects of ATP-Sensitive Potassium Channels Opener Diazoxide

Акопова¹

2017

J Drug Metab Toxicol

View full text Add to dashboard Cite

Diazoxide (DZ) is a well-known cardioprotective drug capable of mimicking ischemic preconditioning. Being primarily a pharmacological opener of mitochondrial ATP-sensitive potassium channels (mK ATP channels), DZ is known to produce multiple side effects because of its interactions with different cellular targets (such as plasma membrane K ATP channels, F 0 F 1 ATP synthase, succinate dehydrogenase and others), capable of confounding an understanding of direct bioenergetic effects of mK ATP channels opening in mitochondria. In this review direct and offtarget effects of DZ were discussed. The emphasis was made on molecular basis of DZ interaction with K ATP channels and different K ATP channels isoforms sensitivity to this drug. The present knowledge on DZ interaction with mK ATP channels is outlined as well as DZ interactions with other molecular targets affecting mitochondrial functions and bioenergetics. Conclusion was reached that high sensitivity of mK ATP channel to DZ allows for avoiding offtarget effects of this drug in studies on isolated mitochondria, which makes it a useful tool in an appraisal of diverse functional effects of mK ATP channel opening.

show abstract

Neuronal KATP channels mediate hypoxic preconditioning and reduce subsequent neonatal hypoxic–ischemic brain injury

Cited by 68 publications

References 49 publications

Cerebrovascular Safety of Sulfonylureas: The Role of KATP Channels in Neuroprotection and the Risk of Stroke in Patients With Type 2 Diabetes

Cerebrovascular Safety of Sulfonylureas: The Role of KATP Channels in Neuroprotection and the Risk of Stroke in Patients With Type 2 Diabetes

Effects of marine compound xyloketal B on neuroprotection and potential drug development

Direct and Off-Target Effects of ATP-Sensitive Potassium Channels Opener Diazoxide

Contact Info

Product

Resources

About