Unravelling the neuroprotective mechanisms of carotenes in differentiated human neural cells: Biochemical and proteomic approaches

Kasthuri Bai Magalingam; Sushela Devi Somanath; Nagaraja Haleagrahara; Kanga Rani Selvaduray; Ammu Kutty Radhakrishnan

doi:10.1016/j.fochms.2022.100088

Unravelling the neuroprotective mechanisms of carotenes in differentiated human neural cells: Biochemical and proteomic approaches

Food Chem (Oxf). 2022 Feb 14:4:100088. doi: 10.1016/j.fochms.2022.100088. eCollection 2022 Jul 30.

Authors

Kasthuri Bai Magalingam¹, Sushela Devi Somanath², Nagaraja Haleagrahara³, Kanga Rani Selvaduray⁴, Ammu Kutty Radhakrishnan¹

Affiliations

¹ Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia.
² Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
³ College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
⁴ Development and Advisory Services, Malaysian Palm Oil Board, Kajang, Malaysia.

Abstract

Carotenoids, fat-soluble pigments found ubiquitously in plants and fruits, have been reported to exert significant neuroprotective effects against free radicals. However, the neuroprotective effects of total mixed carotenes complex (TMC) derived from virgin crude palm oil have not been studied extensively. Therefore, the present study was designed to establish the neuroprotective role of TMC on differentiated human neural cells against 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. The human neural cells were differentiated using retinoic acid for six days. Then, the differentiated neural cells were pre-treated for 24 hr with TMC before exposure to 6-OHDA. TMC pre-treated neurons showed significant alleviation of 6-OHDA-induced cytotoxicity as evidenced by enhanced activity of the superoxide dismutase (SOD) and catalase (CAT) enzymes. Furthermore, TMC elevated the levels of intra-neuronal dopamine and tyrosine hydroxylase (TH) in differentiated neural cells. The 6-OHDA induced overexpression of α-synuclein was significantly hindered in neural cells pre-treated with TMC. In proteomic analysis, TMC altered the expression of ribosomal proteins, α/β isotypes of tubulins, protein disulphide isomerases (PDI) and heat shock proteins (HSP) in differentiated human neural cells. The natural palm phytonutrient TMC is a potent antioxidant with significant neuroprotective effects against free radical-induced oxidative stress.

Keywords: 6-OHDA, 6-hydroxydopamine; 6-hydroxydopamine; AD, Alzheimer’s disease; BCM, beta-carotene-15,15′-monooxygenase; CAT, catalase; DRD2, dopamine receptor D2; Dopamine; ER, endoplasmic reticulum; GO, gene ontology; HSP, Heat shock protein; HSPA9, Heat shock protein family A (HSP70) member 9; HSPD1, Heat shock protein family D (HSP60) member 1; KEGG, Kyoto Encyclopedia of Genes and Genomes; LC-MS/MS, liquid chromatography-double mass spectrometry; LDH, lactate dehydrogenase; MCODE, minimal common oncology data elements; MS, mass spectrometry; Mixed carotene; PD, Parkinson's disease; PDI, protein disulphide isomerases; PHB2, prohibitin 2; PPI, protein–protein interaction; RAN, Ras-related nuclear protein; ROS, reactive oxygen species; RPs, ribosomal proteins; SH-SY5Y neuroblastoma cells; SOD, superoxide dismutase; TH, tyrosine hydroxylase; TMC, total mixed carotene complex.