Cargando…

Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection

Japanese encephalitis virus (JEV) infection induces uncontrolled neuronal apoptosis, leading to irreversible brain damage. However, the mechanism of JEV-induced neuronal apoptosis has not been clearly elucidated. This study aimed to investigate both virus replication and neuronal cell apoptosis duri...

Descripción completa

Detalles Bibliográficos
Autores principales: Wongchitrat, Prapimpun, Samutpong, Arisara, Lerdsamran, Hatairat, Prasertsopon, Jarunee, Yasawong, Montri, Govitrapong, Piyarat, Puthavathana, Pilaipan, Kitidee, Kuntida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834179/
https://www.ncbi.nlm.nih.gov/pubmed/31658698
http://dx.doi.org/10.3390/ijms20205016
_version_ 1783466437293113344
author Wongchitrat, Prapimpun
Samutpong, Arisara
Lerdsamran, Hatairat
Prasertsopon, Jarunee
Yasawong, Montri
Govitrapong, Piyarat
Puthavathana, Pilaipan
Kitidee, Kuntida
author_facet Wongchitrat, Prapimpun
Samutpong, Arisara
Lerdsamran, Hatairat
Prasertsopon, Jarunee
Yasawong, Montri
Govitrapong, Piyarat
Puthavathana, Pilaipan
Kitidee, Kuntida
author_sort Wongchitrat, Prapimpun
collection PubMed
description Japanese encephalitis virus (JEV) infection induces uncontrolled neuronal apoptosis, leading to irreversible brain damage. However, the mechanism of JEV-induced neuronal apoptosis has not been clearly elucidated. This study aimed to investigate both virus replication and neuronal cell apoptosis during JEV infection in human neuroblastoma SH-SY5Y cells. As a result, the kinetic productions of new viral progeny were time- and dose-dependent. The stimulation of SH-SY5Y cell apoptosis was dependent on the multiplicity of infections (MOIs) and infection periods, particularly during the late period of infection. Interestingly, we observed that of full-length Bax (p21 Bax) level started to decrease, which corresponded to the increased level of its cleaved form (p18 Bax). The formation of p18 Bax resulting in cytochrome c release into the cytosol appeared to correlate with JEV-induced apoptotic cell death together with the activation of caspase-3/7 activity, especially during the late stage of a robust viral infection. Therefore, our results suggest another possible mechanism of JEV-induced apoptotic cell death via the induction of the proteolysis of endogenous p21 Bax to generate p18 Bax. This finding could be a new avenue to facilitate novel drug discovery for the further development of therapeutic treatments that could relieve neuronal damage from JEV infection.
format Online
Article
Text
id pubmed-6834179
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68341792019-11-25 Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection Wongchitrat, Prapimpun Samutpong, Arisara Lerdsamran, Hatairat Prasertsopon, Jarunee Yasawong, Montri Govitrapong, Piyarat Puthavathana, Pilaipan Kitidee, Kuntida Int J Mol Sci Article Japanese encephalitis virus (JEV) infection induces uncontrolled neuronal apoptosis, leading to irreversible brain damage. However, the mechanism of JEV-induced neuronal apoptosis has not been clearly elucidated. This study aimed to investigate both virus replication and neuronal cell apoptosis during JEV infection in human neuroblastoma SH-SY5Y cells. As a result, the kinetic productions of new viral progeny were time- and dose-dependent. The stimulation of SH-SY5Y cell apoptosis was dependent on the multiplicity of infections (MOIs) and infection periods, particularly during the late period of infection. Interestingly, we observed that of full-length Bax (p21 Bax) level started to decrease, which corresponded to the increased level of its cleaved form (p18 Bax). The formation of p18 Bax resulting in cytochrome c release into the cytosol appeared to correlate with JEV-induced apoptotic cell death together with the activation of caspase-3/7 activity, especially during the late stage of a robust viral infection. Therefore, our results suggest another possible mechanism of JEV-induced apoptotic cell death via the induction of the proteolysis of endogenous p21 Bax to generate p18 Bax. This finding could be a new avenue to facilitate novel drug discovery for the further development of therapeutic treatments that could relieve neuronal damage from JEV infection. MDPI 2019-10-10 /pmc/articles/PMC6834179/ /pubmed/31658698 http://dx.doi.org/10.3390/ijms20205016 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wongchitrat, Prapimpun
Samutpong, Arisara
Lerdsamran, Hatairat
Prasertsopon, Jarunee
Yasawong, Montri
Govitrapong, Piyarat
Puthavathana, Pilaipan
Kitidee, Kuntida
Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection
title Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection
title_full Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection
title_fullStr Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection
title_full_unstemmed Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection
title_short Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection
title_sort elevation of cleaved p18 bax levels associated with the kinetics of neuronal cell death during japanese encephalitis virus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834179/
https://www.ncbi.nlm.nih.gov/pubmed/31658698
http://dx.doi.org/10.3390/ijms20205016
work_keys_str_mv AT wongchitratprapimpun elevationofcleavedp18baxlevelsassociatedwiththekineticsofneuronalcelldeathduringjapaneseencephalitisvirusinfection
AT samutpongarisara elevationofcleavedp18baxlevelsassociatedwiththekineticsofneuronalcelldeathduringjapaneseencephalitisvirusinfection
AT lerdsamranhatairat elevationofcleavedp18baxlevelsassociatedwiththekineticsofneuronalcelldeathduringjapaneseencephalitisvirusinfection
AT prasertsoponjarunee elevationofcleavedp18baxlevelsassociatedwiththekineticsofneuronalcelldeathduringjapaneseencephalitisvirusinfection
AT yasawongmontri elevationofcleavedp18baxlevelsassociatedwiththekineticsofneuronalcelldeathduringjapaneseencephalitisvirusinfection
AT govitrapongpiyarat elevationofcleavedp18baxlevelsassociatedwiththekineticsofneuronalcelldeathduringjapaneseencephalitisvirusinfection
AT puthavathanapilaipan elevationofcleavedp18baxlevelsassociatedwiththekineticsofneuronalcelldeathduringjapaneseencephalitisvirusinfection
AT kitideekuntida elevationofcleavedp18baxlevelsassociatedwiththekineticsofneuronalcelldeathduringjapaneseencephalitisvirusinfection