+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity by Activating the AMPK/SIRT1, MAPK/Erk, and PI3k/Akt Signaling Pathways



Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity by Activating the AMPK/SIRT1, MAPK/Erk, and PI3k/Akt Signaling Pathways



Neurotoxicity Research 2019



Peripheral sensory neuropathy (PSN) is a well-known side effect of cisplatin characterized by axonal damage. In the early stage of neurotoxicity, cisplatin affects proteins that modulate neurite outgrowth and neuroplasticity, without inducing mitochondrial damage or apoptosis. There are no preventive therapies for cisplatin-induced peripheral neuropathy; therefore, measures to improve axonal growth and connectivity would be beneficial. Caffeic acid phenethyl ester (CAPE) is a bioactive component of propolis with neurotrophic and neuroprotective activities. We have recently showed that CAPE protects against cisplatin-induced neurotoxicity by activating NGF high-affinity receptors (trkA) and inducing neuroplasticity. We have now assessed other potential early targets of cisplatin and additional mechanisms involved in the neuroprotection of CAPE. Cisplatin reduced axonal cytoskeletal proteins (F-actin and β-III-tubulin) without inducing oxidative damage in PC12 cells. It also reduced energy-related proteins (AMPK α, p-AMPK α, and SIRT1) and glucose uptake. At this stage of neurotoxicity, glutamate excitotoxicity is not involved in the toxicity of cisplatin. CAPE attenuated the downregulation of the cytoskeleton and energy-related markers as well as SIRT1 and phosphorylated AMPK α. Moreover, the neuroprotective mechanism of CAPE also involves the activation of the neurotrophic signaling pathways MAPK/Erk and PI3k/Akt. The PI3K/Akt pathway is involved in the upregulation of SIRT1 induced by CAPE, but not in the upregulation of cytoskeletal proteins. Altogether, these findings suggest that the neuroprotective effect of CAPE against cisplatin-induced neurotoxicity involves both (a) a neurotrophic mechanism that mimics the mechanism triggered by the NGF itself and (b) a non-neurotrophic mechanism that upregulates the cytoskeletal proteins.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 066719345

Download citation: RISBibTeXText

PMID: 31016689

DOI: 10.1007/s12640-019-00042-w


Related references

Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells from Cisplatin-Induced Neurotoxicity by Activating the NGF-Signaling Pathway. Neurotoxicity Research 34(1): 32-46, 2017

Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane‑induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt signaling pathways. Molecular Medicine Reports 14(4): 3403-3412, 2017

Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins. Neurotoxicology 45: 131-138, 2015

Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit. Experimental and Toxicologic Pathology 62(1): 45-52, 2010

Caffeic acid phenethyl ester reduces the secretion of vascular endothelial growth factor through the inhibition of the ROS, PI3K and HIF-1α signaling pathways in human retinal pigment epithelial cells under hypoxic conditions. International Journal of Molecular Medicine 35(5): 1419-1426, 2015

Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells. Neuroscience Letters 535: 146-151, 2013

CAPE (caffeic acid phenethyl ester) stimulates glucose uptake through AMPK (AMP-activated protein kinase) activation in skeletal muscle cells. Biochemical and Biophysical Research Communications 361(4): 854-858, 2007

Protective effect of caffeic acid phenethyl ester (CAPE) administration on cisplatin-induced oxidative damage to liver in rat. Cell Biochemistry and Function 24(4): 357-361, 2006

Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats. Molecular and Cellular Biochemistry 312(1-2): 39-46, 2008

Caffeic acid phenethyl ester (CAPE) protects rat skeletal muscle against ischemia-reperfusion-induced oxidative stress. Vascular Pharmacology 47(2-3): 108-112, 2007

Assesment the role of oxidative stress and efficacy of caffeic acid phenethyl ester (CAPE) on neurotoxicity induced by isoniazid and ethambutol in a rat model. European Review for Medical and Pharmacological Sciences 18(19): 2953-2959, 2015

Inhibition of AMPK-associated autophagy enhances caffeic acid phenethyl ester-induced cell death in C6 glioma cells. Planta Medica 77(9): 907-914, 2012

Synthesis of a series of caffeic acid phenethyl amide (CAPA) fluorinated derivatives: comparison of cytoprotective effects to caffeic acid phenethyl ester (CAPE). Bioorganic and Medicinal Chemistry 18(14): 5032-5038, 2010

Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells. Pharmaceutical Biology 52(7): 926-932, 2015

Caffeic acid phenethyl ester (CAPE) protects against acute urogenital injury following pneumoperitoneum in the rat. Renal Failure 36(1): 98-103, 2014