Cytoprotection against Hypoxic and/or MPP+ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3

Xu, Yuan; Zhi, Feng; Shao, Naiyuan; Wang, Rong; Yang, Yilin; Xia, Ying

doi:10.3390/ijms17081179

Open AccessArticle

Cytoprotection against Hypoxic and/or MPP⁺ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3

by

Yuan Xu

^1,†

,

Feng Zhi

^1,†,

Naiyuan Shao

¹,

Rong Wang

¹,

Yilin Yang

^1,* and

Ying Xia

^2,*

¹

Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, China

²

Department of Neurosurgery, The University of Texas McGovern Medical School, Houston, TX 77030, USA

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2016, 17(8), 1179; https://doi.org/10.3390/ijms17081179

Submission received: 5 June 2016 / Revised: 13 July 2016 / Accepted: 13 July 2016 / Published: 9 August 2016

(This article belongs to the Special Issue Neuroprotective Strategies 2016)

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Abstract

The pathological changes of Parkinson’s disease (PD) are, at least partially, associated with the dysregulation of PTEN-induced putative kinase 1 (PINK1) and caspase 3. Since hypoxic and neurotoxic insults are underlying causes of PD, and since δ-opioid receptor (DOR) is neuroprotective against hypoxic/ischemic insults, we sought to determine whether DOR activation could protect the cells from damage induced by hypoxia and/or MPP⁺ by regulating PINK1 and caspase 3 expressions. We exposed PC12 cells to either severe hypoxia (0.5%–1% O₂) for 24–48 h or to MPP⁺ at different concentrations (0.5, 1, 2 mM) and then detected the levels of PINK1 and cleaved caspase 3. Both hypoxia and MPP⁺ reduced cell viability, progressively suppressed the expression of PINK1 and increased the cleaved caspase 3. DOR activation using UFP-512, effectively protected the cells from hypoxia and/or MPP⁺ induced injury, reversed the reduction in PINK1 protein and significantly attenuated the increase in the cleaved caspase 3. On the other hand, the application of DOR antagonist, naltrindole, greatly decreased cell viability and increased cleaved caspase 3. These findings suggest that DOR is cytoprotective against both hypoxia and MPP⁺ through the regulation of PINK1 and caspase 3 pathways.

Keywords: Parkinson’s disease; δ-opioid receptor; cytoprotection; hypoxia; MPP⁺; PINK1; caspase 3

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MDPI and ACS Style

Xu, Y.; Zhi, F.; Shao, N.; Wang, R.; Yang, Y.; Xia, Y. Cytoprotection against Hypoxic and/or MPP⁺ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3. Int. J. Mol. Sci. 2016, 17, 1179. https://doi.org/10.3390/ijms17081179

AMA Style

Xu Y, Zhi F, Shao N, Wang R, Yang Y, Xia Y. Cytoprotection against Hypoxic and/or MPP⁺ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3. International Journal of Molecular Sciences. 2016; 17(8):1179. https://doi.org/10.3390/ijms17081179

Chicago/Turabian Style

Xu, Yuan, Feng Zhi, Naiyuan Shao, Rong Wang, Yilin Yang, and Ying Xia. 2016. "Cytoprotection against Hypoxic and/or MPP⁺ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3" International Journal of Molecular Sciences 17, no. 8: 1179. https://doi.org/10.3390/ijms17081179

APA Style

Xu, Y., Zhi, F., Shao, N., Wang, R., Yang, Y., & Xia, Y. (2016). Cytoprotection against Hypoxic and/or MPP⁺ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3. International Journal of Molecular Sciences, 17(8), 1179. https://doi.org/10.3390/ijms17081179

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Cytoprotection against Hypoxic and/or MPP⁺ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3

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