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Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells.
Neurochem Int. 2011 Mar; 58(4):533-41.NI

Abstract

We investigated the mechanisms underlying the protective effects of loganin against hydrogen peroxide (H(2)O(2))-induced neuronal toxicity in SH-SY5Y cells. The neuroprotective effect of loganin was investigated by treating SH-SY5Y cells with H(2)O(2) and then measuring the reduction in H(2)O(2)-induced apoptosis using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. Following H(2)O(2) exposure, Hoechst 33258 staining indicated nuclear condensation in a large proportion of SH-SY5Y cells, along with an increase in reactive oxygen species (ROS) production and an intracellular decrease in mitochondria membrane potential (MMP). Loganin was effective in attenuating all the above-stated phenotypes induced by H(2)O(2). Pretreatment with loganin significantly increased cell viability, reduced H(2)O(2)-induced LDH release and ROS production, and effectively increased intracellular MMP. Pretreatment with loganin also significantly decreased the nuclear condensation induced by H(2)O(2). Western blot data revealed that loganin inhibited the H(2)O(2)-induced up-regulation of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3, increased the H(2)O(2)-induced decrease in the Bcl-2/Bax ratio, and attenuated the H(2)O(2)-induced release of cytochrome c from mitochondria to the cytosol. Furthermore, pretreatment with loganin significantly attenuated the H(2)O(2)-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase 1/2 (ERK 1/2). These results suggest that the protective effects of loganin against H(2)O(2)-induced apoptosis may be due to a decrease in the Bcl-2/Bax ratio expression due to the inhibition of the phosphorylation of JNK, p38, and ERK 1/2 MAPKs. Loganin's neuroprotective properties indicate that this compound may be a potential therapeutic agent for the treatment of neurodegenerative diseases.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21241762

Citation

Kwon, Seung-Hwan, et al. "Loganin Protects Against Hydrogen Peroxide-induced Apoptosis By Inhibiting Phosphorylation of JNK, P38, and ERK 1/2 MAPKs in SH-SY5Y Cells." Neurochemistry International, vol. 58, no. 4, 2011, pp. 533-41.
Kwon SH, Kim JA, Hong SI, et al. Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells. Neurochem Int. 2011;58(4):533-41.
Kwon, S. H., Kim, J. A., Hong, S. I., Jung, Y. H., Kim, H. C., Lee, S. Y., & Jang, C. G. (2011). Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells. Neurochemistry International, 58(4), 533-41. https://doi.org/10.1016/j.neuint.2011.01.012
Kwon SH, et al. Loganin Protects Against Hydrogen Peroxide-induced Apoptosis By Inhibiting Phosphorylation of JNK, P38, and ERK 1/2 MAPKs in SH-SY5Y Cells. Neurochem Int. 2011;58(4):533-41. PubMed PMID: 21241762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells. AU - Kwon,Seung-Hwan, AU - Kim,Ji-Ah, AU - Hong,Sa-Ik, AU - Jung,Yang-Hee, AU - Kim,Hyoung-Chun, AU - Lee,Seok-Yong, AU - Jang,Choon-Gon, Y1 - 2011/01/15/ PY - 2010/05/22/received PY - 2011/01/04/revised PY - 2011/01/11/accepted PY - 2011/1/19/entrez PY - 2011/1/19/pubmed PY - 2011/6/18/medline SP - 533 EP - 41 JF - Neurochemistry international JO - Neurochem Int VL - 58 IS - 4 N2 - We investigated the mechanisms underlying the protective effects of loganin against hydrogen peroxide (H(2)O(2))-induced neuronal toxicity in SH-SY5Y cells. The neuroprotective effect of loganin was investigated by treating SH-SY5Y cells with H(2)O(2) and then measuring the reduction in H(2)O(2)-induced apoptosis using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. Following H(2)O(2) exposure, Hoechst 33258 staining indicated nuclear condensation in a large proportion of SH-SY5Y cells, along with an increase in reactive oxygen species (ROS) production and an intracellular decrease in mitochondria membrane potential (MMP). Loganin was effective in attenuating all the above-stated phenotypes induced by H(2)O(2). Pretreatment with loganin significantly increased cell viability, reduced H(2)O(2)-induced LDH release and ROS production, and effectively increased intracellular MMP. Pretreatment with loganin also significantly decreased the nuclear condensation induced by H(2)O(2). Western blot data revealed that loganin inhibited the H(2)O(2)-induced up-regulation of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3, increased the H(2)O(2)-induced decrease in the Bcl-2/Bax ratio, and attenuated the H(2)O(2)-induced release of cytochrome c from mitochondria to the cytosol. Furthermore, pretreatment with loganin significantly attenuated the H(2)O(2)-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase 1/2 (ERK 1/2). These results suggest that the protective effects of loganin against H(2)O(2)-induced apoptosis may be due to a decrease in the Bcl-2/Bax ratio expression due to the inhibition of the phosphorylation of JNK, p38, and ERK 1/2 MAPKs. Loganin's neuroprotective properties indicate that this compound may be a potential therapeutic agent for the treatment of neurodegenerative diseases. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/21241762/Loganin_protects_against_hydrogen_peroxide_induced_apoptosis_by_inhibiting_phosphorylation_of_JNK_p38_and_ERK_1/2_MAPKs_in_SH_SY5Y_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(11)00014-3 DB - PRIME DP - Unbound Medicine ER -