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A Cystine-Rich Whey Supplement (Immunocal®) Provides Neuroprotection From Diverse Oxidative Stress-Inducing Agents

Aimee N Winter, Erika K Ross, Vamsi Daliparthi, Whitney A Sumner, Danielle M Kirchhof, Evan Manning, Heather M Wilkins, Daniel A Linseman

Oxid Med Cell Longev. 2017;2017:3103272.

PMID: 28894506

Abstract:

Oxidative stress is a principal mechanism underlying the pathophysiology of neurodegeneration. Therefore, nutritional enhancement of endogenous antioxidant defenses may represent a viable treatment option. We investigated the neuroprotective properties of a unique whey protein supplement (Immunocal®) that provides an essential precursor (cystine) for synthesis of the endogenous antioxidant, glutathione (GSH). Primary cultures of rat cerebellar granule neurons (CGNs), NSC34 motor neuronal cells, or HT22 hippocampal cells were preincubated in medium containing Immunocal and then subsequently treated with agents known to induce oxidative stress. Immunocal protected CGNs against neurotoxicity induced by the Bcl-2 inhibitor, HA14-1, the nitric oxide donor, sodium nitroprusside, CuCl2, and AlCl3. Immunocal also significantly reduced NSC34 cell death due to either H2O2 or glutamate and mitigated toxicity in HT22 cells overexpressing β-amyloid1-42. The neuroprotective effects of Immunocal were blocked by inhibition of γ-glutamyl-cysteine ligase, demonstrating dependence on de novo GSH synthesis. These findings indicate that sustaining GSH with Immunocal significantly protects neurons against diverse inducers of oxidative stress. Thus, Immunocal is a nutritional supplement worthy of testing in preclinical animal models of neurodegeneration and in future clinical trials of patients afflicted by these diseases.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP107761422-B β-Amyloid Peptide (1-42), Rat β-Amyloid Peptide (1-42), Rat 107761-42-2 Price
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