Iptakalim protects PC12 cell against H2O2-induced oxidative injury via opening mitochondrial ATP-sensitive potassium channel
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Published on: November 18, 2022
Yi Chai1, Ling Niu, Xiu-Lan Sun
1Laboratory of Neuropharmacology, Department of Anatomy, Histology and Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
Abstract:
The final common pathway in the demise of dopaminergic neurons in Parkinson's disease may involve oxidative stress and excitotoxicity. In this study, we examined the neuroprotective effects of a novel ATP-sensitive potassium channel (K(ATP)) opener, iptakalim (IPT), against H(2)O(2)-induced cytotoxicity in rat dopaminergic PC12 cells. Pretreatment with IPT could attenuate increased extracellular glutamate levels and inhibit calcium influxing induced by H(2)O(2). Moreover, IPT regulated the expressions of bcl-2 and bax which were responsible for inhibiting apoptosis in PC12 cells. These protective effects of IPT were abolished by selective mitoK(ATP) channel blocker 5-hydroxydecanoate. Therefore, IPT can protect PC12 cells against H(2)O(2)-induced oxidative injury via activating mitoK(ATP) channel.
Insights
Iptakalim (IPT), an ATP-sensitive potassium channel opener, protects rat dopaminergic cells from oxidative stress. It achieves this by activating mitochondrial K(ATP) channels, reducing cell death and preserving neuron function.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Oxidative stress and excitotoxicity are implicated in dopaminergic neuron loss in Parkinson's disease.
- ATP-sensitive potassium channels (K(ATP)) are potential therapeutic targets for neuroprotection.
Purpose of the Study:
- To investigate the neuroprotective effects of iptakalim (IPT), a novel K(ATP) channel opener.
- To determine the mechanism by which IPT protects dopaminergic PC12 cells against hydrogen peroxide (H(2)O(2))-induced injury.
Main Methods:
- PC12 cells were pretreated with IPT and exposed to H(2)O(2) to induce oxidative stress.
- Extracellular glutamate levels, calcium influx, and apoptosis-related gene expressions (bcl-2, bax) were measured.
- The role of mitochondrial K(ATP) channels was assessed using a selective blocker, 5-hydroxydecanoate.
Main Results:
- IPT pretreatment attenuated H(2)O(2)-induced increases in extracellular glutamate and inhibited calcium influx.
- IPT modulated the expression of bcl-2 and bax, suggesting inhibition of apoptosis.
- The protective effects of IPT were reversed by the mitoK(ATP) channel blocker 5-hydroxydecanoate.
Conclusions:
- Iptakalim (IPT) demonstrates significant neuroprotective effects against H(2)O(2)-induced oxidative injury in PC12 cells.
- These protective effects are mediated through the activation of mitochondrial K(ATP) channels (mitoK(ATP)).
- IPT represents a potential therapeutic agent for conditions involving oxidative stress in dopaminergic neurons, such as Parkinson's disease.
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