Selenium-containing protein from selenium-enriched Spirulina platensis antagonizes oxygen glucose deprivation-induced neurotoxicity by inhibiting ROS-mediated oxidative damage through regulating MPTP opening

Abstract

Context

Selenium-containing protein from selenium-enriched Spirulina platensis (Se-SP) (syn. Arthrospira platensis [Microcoleaceae]) showed novel antioxidant activity. However, the protective effect of Se-SP against oxygen glucose deprivation (OGD)-induced neural apoptosis has not been reported yet.

Objective

To verify whether Se-SP can inhibit OGD-induced neural apoptosis and explore the underlying mechanism.

Materials and methods

Primary hippocampal neurons were separated from Sprague–Dawley (SD) rats. 95% N₂ + 5% CO₂ were employed to establish OGD model. Neurons were treated with 5 and 10 µg/mL Se-SP under OGD condition for 6 h. Neurons without treatment were the control group. Neural viability and apoptosis were detected by MTT, immunofluorescence and western blotting methods.

Results

Se-SP significantly improved neuronal viability (from 57.2% to 94.5%) and inhibited apoptosis in OGD-treated primary neurons (from 45.6% to 6.3%), followed by improved neuronal morphology and caspases activation. Se-SP co-treatment also effectively suppressed OGD-induced DNA damage by inhibiting ROS accumulation in neurons (from 225.6% to 106.3%). Additionally, mitochondrial dysfunction was also markedly improved by Se-SP co-treatment via balancing Bcl-2 family expression. Moreover, inhibition of mitochondrial permeability transition pore (MPTP) by CsA (an MPTP inhibitor) dramatically attenuated OGD-induced ROS generation (from 100% to 56.2%), oxidative damage, mitochondrial membrane potential (MPP) loss (from 7.5% to 44.3%), and eventually reversed the neuronal toxicity and apoptosis (from 57.4% to 79.6%).

Discussion and conclusions

Se-SP showed enhanced potential to inhibit OGD-induced neurotoxicity and apoptosis by inhibiting ROS-mediated oxidative damage through regulating MPTP opening, indicating that selenium-containing protein showed broad application in the chemoprevention and chemotherapy against human ischaemic brain injury.

Keywords:

• Ischaemic brain injury
• apoptosis
• neurons
• mitochondrial dysfunction

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by Medicine and Health Care Science & Technology Development Program in Shandong province [2019WS128, 2019WS214] and Open Project of Guangdong Key lab of Marine Materia Medica, China [LMM-2019-3].