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Regulation of AKT/AMPK signaling, autophagy and mitigation of apoptosis in Rutin-pretreated SH-SY5Y cells exposed to MPP.
Metab Brain Dis. 2021 02; 36(2):315-326.MB

Abstract

Accumulating evidence suggest that apoptosis, autophagy and dysregulation of signaling pathways are common mechanisms involved in Parkinson's disease (PD) pathogenesis, and thus development of therapeutic agents targeting these mechanisms may be useful for the treatment of this disease. Although rutin (a bioflavonoid) is reported to have pharmacological benefits such as antioxidant, anti-inflammatory and antitumor activities, there are very few reports on the activity of this compound in 1-methyl-4-phenylpyridinium (MPP+)-induced PD models. Accordingly, we investigated the effects of rutin on apoptosis, autophagy and cell signaling markers (AKT/AMPK) in SH-SY5Y cells exposed to MPP+. Results show reduced changes in nuclear morphology and mitigation of caspase 3/7 and 9 activities in rutin pre-treated cells exposed to MPP+. Likewise, rutin regulated cell signaling pathways (AKT/AMPK) and significantly decreased protein expression levels of cleaved PARP, cytochrome c, LC3-II and p62. Also, rutin significantly increased protein expression levels of full-length caspase 3 in SH-SY5Y cells treated with MPP+. Transmission electron microscope (TEM) images demonstrated a reduction in autophagosomes in rutin-pretreated SH-SY5Y cells exposed to MPP+. These results provide experimental support for rutin's neuroprotective activity against MPP+-induced toxicity in SH-SY5Y cells, which is as a promising therapeutic agent for clinical trials in humans.

Authors+Show Affiliations

Department of Medical Biosciences, University of the Western Cape, Robert Sobukwe Road, Private Bag X17, Bellville, 7535, South Africa. Department of Anatomy, School of Basic Medical Sciences, University of Benin, Benin City, Edo State, Nigeria.Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.Department of Medical Biosciences, University of the Western Cape, Robert Sobukwe Road, Private Bag X17, Bellville, 7535, South Africa.Department of Medical Biosciences, University of the Western Cape, Robert Sobukwe Road, Private Bag X17, Bellville, 7535, South Africa. oekpo@uwc.ac.za.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33146846

Citation

Enogieru, Adaze Bijou, et al. "Regulation of AKT/AMPK Signaling, Autophagy and Mitigation of Apoptosis in Rutin-pretreated SH-SY5Y Cells Exposed to MPP." Metabolic Brain Disease, vol. 36, no. 2, 2021, pp. 315-326.
Enogieru AB, Haylett W, Hiss DC, et al. Regulation of AKT/AMPK signaling, autophagy and mitigation of apoptosis in Rutin-pretreated SH-SY5Y cells exposed to MPP. Metab Brain Dis. 2021;36(2):315-326.
Enogieru, A. B., Haylett, W., Hiss, D. C., & Ekpo, O. E. (2021). Regulation of AKT/AMPK signaling, autophagy and mitigation of apoptosis in Rutin-pretreated SH-SY5Y cells exposed to MPP. Metabolic Brain Disease, 36(2), 315-326. https://doi.org/10.1007/s11011-020-00641-z
Enogieru AB, et al. Regulation of AKT/AMPK Signaling, Autophagy and Mitigation of Apoptosis in Rutin-pretreated SH-SY5Y Cells Exposed to MPP. Metab Brain Dis. 2021;36(2):315-326. PubMed PMID: 33146846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of AKT/AMPK signaling, autophagy and mitigation of apoptosis in Rutin-pretreated SH-SY5Y cells exposed to MPP. AU - Enogieru,Adaze Bijou, AU - Haylett,William, AU - Hiss,Donavon Charles, AU - Ekpo,Okobi Eko, Y1 - 2020/11/04/ PY - 2020/08/17/received PY - 2020/10/30/accepted PY - 2020/11/5/pubmed PY - 2021/10/6/medline PY - 2020/11/4/entrez KW - Apoptosis KW - Autophagy KW - Cell signaling KW - MPP KW - Rutin SP - 315 EP - 326 JF - Metabolic brain disease JO - Metab Brain Dis VL - 36 IS - 2 N2 - Accumulating evidence suggest that apoptosis, autophagy and dysregulation of signaling pathways are common mechanisms involved in Parkinson's disease (PD) pathogenesis, and thus development of therapeutic agents targeting these mechanisms may be useful for the treatment of this disease. Although rutin (a bioflavonoid) is reported to have pharmacological benefits such as antioxidant, anti-inflammatory and antitumor activities, there are very few reports on the activity of this compound in 1-methyl-4-phenylpyridinium (MPP+)-induced PD models. Accordingly, we investigated the effects of rutin on apoptosis, autophagy and cell signaling markers (AKT/AMPK) in SH-SY5Y cells exposed to MPP+. Results show reduced changes in nuclear morphology and mitigation of caspase 3/7 and 9 activities in rutin pre-treated cells exposed to MPP+. Likewise, rutin regulated cell signaling pathways (AKT/AMPK) and significantly decreased protein expression levels of cleaved PARP, cytochrome c, LC3-II and p62. Also, rutin significantly increased protein expression levels of full-length caspase 3 in SH-SY5Y cells treated with MPP+. Transmission electron microscope (TEM) images demonstrated a reduction in autophagosomes in rutin-pretreated SH-SY5Y cells exposed to MPP+. These results provide experimental support for rutin's neuroprotective activity against MPP+-induced toxicity in SH-SY5Y cells, which is as a promising therapeutic agent for clinical trials in humans. SN - 1573-7365 UR - https://www.unboundmedicine.com/medline/citation/33146846/Regulation_of_AKT/AMPK_signaling_autophagy_and_mitigation_of_apoptosis_in_Rutin_pretreated_SH_SY5Y_cells_exposed_to_MPP_ L2 - https://doi.org/10.1007/s11011-020-00641-z DB - PRIME DP - Unbound Medicine ER -