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PACAP Protects Against Ethanol and Nicotine Toxicity in SH-SY5Y Cells: Implications for Drinking-Smoking Co-morbidity

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Abstract

The detrimental effects of heavy drinking and smoking are multiplied when the two are combined. Treatment modalities for each and especially for the combination are very limited. Although in low concentration, alcohol and nicotine, each may have beneficial effects including neuroprotection, their combination, instead of providing additive protection, may actually lead to toxicity in cell cultures. Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous 38 amino-acid peptide with demonstrated protection against neuronal injury, trauma as well as various endogenous and exogenous toxic agents. The aim of this study was to investigate whether PACAP may also protect against toxicity induced by high alcohol, high nicotine, or the combination of low alcohol and nicotine concentrations, and if so, whether this effect was mediated via PAC1 receptor. We used the neuroblastoma-derived SH-SY5Y cells and applied various colorimetric assays for determination of cell viability or toxicity. Results indicate that PACAP blocks toxicity induced by high alcohol and high nicotine as well as their combination at low concentrations. The effects of PACAP in turn were blocked by the PACAP antagonist (PACAP 6-38), indicating involvement of the PACAP receptor PAC1 and possibly vasoactive intestinal peptide (VIP) receptors in PACAP’s protection. Moreover, no combined toxicity of low alcohol and low nicotine could be detected in calcium-free medium. These findings suggest possible beneficial effects of PACAP in preventing alcohol and nicotine toxicity and that calcium contributes to the damage induced by combination of low alcohol and nicotine in SH-SY5Y cells.

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Acknowledgements

Supported by: NIH/NIAAA R03AA022479 (YT); DC-IDDRC 1U54HD090257-01 (YT & ABC); Hungarian Brain Research Program (Grant No. KTIA_13_NAP-A-III/5), TAMOP 4.2.4.A/2-11-1-2012-0001, National Excellence Program and New National Excellence Program of the Ministry of Human Capacities (AT, UNKP-16-3-IV), and Centre for Neuroscience, University of Pecs (RD, AT, SM), GINOP-2.3.2-15-2016-00050 “PEPSYS” (RD, AT, SM), OTKA K104984, K119759) (AT, DR); NIH/NIA 1R25AG047843-01 and 1R03G049288-01A1 (KM), NIH/NIA R21AG047474 and AHA grant-in-aid 16GRNT31030019 (SJK).

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Authors and Affiliations

  1. Department of Basic Sciences, National University of Health Sciences, Pinellas Park, FL, USA

    Sridharan Manavalan

  2. Department of Anatomy, University of Pecs, Pécs, Hungary

    Sridharan Manavalan, Andrea Tamas & Dora Reglodi

  3. Department of Pharmacology, Howard University College of Medicine, 520 W Street, NW, Washington, DC, 20059, USA

    Bruk Getachew & Yousef Tizabi

  4. Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC, USA

    Kebreten F. Manaye & Syed J. Khundmiri

  5. Department of Anatomy, Howard University College of Medicine, Washington, DC, USA

    Antonei B. Csoka & Raechel McKinley

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  1. Sridharan Manavalan
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  2. Bruk Getachew
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  3. Kebreten F. Manaye
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  4. Syed J. Khundmiri
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  9. Yousef Tizabi
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Correspondence to Yousef Tizabi.

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Manavalan, S., Getachew, B., Manaye, K.F. et al. PACAP Protects Against Ethanol and Nicotine Toxicity in SH-SY5Y Cells: Implications for Drinking-Smoking Co-morbidity. Neurotox Res 32, 8–13 (2017). https://doi.org/10.1007/s12640-017-9727-8

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  • DOI: https://doi.org/10.1007/s12640-017-9727-8

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