Up-regulation of HIF-1α is associated with neuroprotective effects of agmatine against rotenone-induced toxicity in differentiated SH-SY5Y cells.

Up-regulation of HIF-1α is associated with neuroprotective effects of agmatine against rotenone-induced toxicity in differentiated SH-SY5Y cells.

Publication date: Jul 10, 2019

Agmatine, a metabolite generated by arginine decarboxylation, has been reported as neuromodulator and neuroactive substance. Several findings suggest that agmatine displays neuroprotective effects in several models of neurodegenerative disorders, such as Parkinson’s disease (PD). It has been hypothesized that biogenic amines may be involved in neuroprotection by scavenging oxygen radicals, thus preventing the generation of oxidative stress. Mitochondrial dysfunction, that leads to a reduction of oxygen consumption, followed by activation of prolyl hydroxylase and decrease of hypoxia-inducible factor 1 alpha (HIF-1α) levels, has been demonstrated to play a role in PD pathogenesis. Using rotenone-treated differentiated SH-SY5Y cells as the in vitro PD model, we here investigated the molecular mechanisms underlying agmatine neuroprotective effects. Our results showed that the preliminary addition of agmatine induces HIF-1α activation, and prevents the rotenone-induced production of free radical species, and the activation of apoptotic pathways by inhibiting mitochondrial membrane potential decrease and caspase 3 as well as cytochrome c increase. Notably, these effects are mediated by HIF-1α, as indicated by experiments using a HIF-1α inhibitor. The present findings suggest that the treatment with agmatine is able to counteract the neuronal cell injury evoked by mitochondrial toxins.

Concepts Keywords
Agmatine Neuroprotection
Apoptotic Hypoxia-inducible factors
Arginine Neurotransmitters
Caspase Amines
Cytochrome Agmatine
Decarboxylation Neurology
Free Radical Oxygen
Hypoxia Transcription factors
Inhibitor Chemistry
Membrane Potential Enzymes
Metabolite Branches of biology
Mitochondrial Neuronal injury
Mitochondrial Membrane Hypoxia in fish
Neurodegenerative Disorders Alpha
Neuromodulator Apoptosis
Neuroprotection
Neuroprotective
Oxidative Stress
Oxygen
Oxygen Radicals
Parkinson
Pathogenesis
Rotenone
Scavenging
Species
Toxicity

Semantics

Type Source Name
pathway BSID Apoptosis
disease MESH hypoxia
pathway BSID Oxidative Stress
disease MESH oxidative stress
drug DRUGBANK Oxygen
disease MESH neurodegenerative disorders
drug DRUGBANK L-Arginine
drug DRUGBANK Rotenone
drug DRUGBANK Agmatine
gene UNIPROT SETD2

Similar

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *