Phycoerythrin Peptide from Pyropia yezoensis Alleviates Endoplasmic Reticulum Stress Caused by Perfluorooctane Sulfonate-Induced Calcium Dysregulation

Abstract

Perfluorooctane sulfonate (PFOS), a stable fluorosurfactant, causes endoplasmic reticulum (ER) stress in the brain. This study was designed to investigate whether a phycoerythrin-derived peptide of Pyropia yezoensis (PYP) reduces PFOS-induced ER stress associated with calcium dysregulation. The protective effects of PYP were determined by cell viability, immunoblotting for ER stress response protein glucose-regulated protein 78 (GRP78) and calcium-dependent protein kinases in rat frontal cortical neurons. PFOS-induced decrease in cell viability was attenuated by PYP pretreatment (1 µg/mL) for 24 h, which was downregulated by inhibiting tropomyosin-receptor kinase B (TrkB). PYP pretreatment downregulated the increase in intracellular calcium levels and phosphorylation of calcium/calmodulin-dependent protein kinase II and c-Jun N-terminal kinase which are associated with a PFOS-induced increase in GRP78. The PFOS-induced increase in GRP78 was downregulated via activation of TrkB receptor-linked extracellular signal-regulated kinases 1/2 (ERK1/2) by PYP pretreatment. Moreover, PYP microinjections (1 µg/kg, 0.54 nmol) attenuated the GRP78 expression in rat prefrontal cortex caused by PFOS (10 mg/kg) exposure for 2 weeks. These findings demonstrate that PYP enhances frontal cortical neuron viability via activation of TrkB receptor-ERK1/2 signaling and attenuation of ER stress in rat prefrontal cortex against PFOS exposure, suggesting that PYP might prevent neuronal dysfunctions caused by PFOS-induced ER stress.

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

“…Dimethylsulfoniopropionate protected against tropodithietic acid-induced cytotoxicity in OLN-93 and N2a cells by lowering the activation of ERK1/2 and induction of HSP32 [ 149 ]. Phycoerythrin-derived peptide isolated from Pyropia yezoensis promoted survivability of frontal cortical neuron by activating TrkB receptor-ERK1/2 signaling and attenuating ER stress in rat prefrontal cortex [ 211 ] and attenuated glutamate-induced ER stress and senescence of rat primary hippocampal neurons [ 212 ]. Stearic acid from Caulerpa racemosa protected against OGD-induced SH-SY5Y cell damage while (8E)-heptadec-8-en-7-one showed moderate neuroprotective activity against Aβ25-35-induced SHSY5Y cell damage [ 213 ].…”

C-phycoerythrin from Phormidium persicinum Prevents Acute Kidney Injury by Attenuating Oxidative and Endoplasmic Reticulum Stress

“…C-PE and C-PC have a similar effect on the IREα pathway, decreasing cell death mediated by caspases 3, 9, and 12 as well as reducing the disruption in p53 activation and the alteration of the Bax/Bcl2 ratio [10,11]. This idea is supported by neurotoxicological models, where C-PE prevents ER stress linked to calcium deregulation and mitochondrial dysfunction [33].…”

Caspase-3/GSDME dependent pyroptosis contributes to offspring lung injury induced by gestational PFOS exposure via PERK/ATF4 signaling

“…Multiple lines of evidence have indicated that ER stress may participate in the PFOS-related cellular injuries and tissue damages, especially for those related to PERK/ATF4 signaling pathway. PFOS was found to upregulate the expression of 78-kDa glucose-regulated protein (GRP78) in the cerebral cortex, leading to neuronal apoptosis (Oh et al 2018 ). Meanwhile, PFOS could selectively activate the PERK/CHOP signaling pathway, in the cerebral cortex of mice, thereby inducing cognitive dysfunction (Zhang et al 2023 ).…”