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Oxicam-derived Non-steroidal Anti-inflammatory Drugs Suppress 1-methyl-4-phenyl Pyridinium-induced Cell Death Via Repression Of Endoplasmic Reticulum Stress Response And Mitochondrial Dysfunction In SH-SY5Y Cells.

T. Omura, Miwa Sasaoka, Gaia Hashimoto, S. Imai, Joe Yamamoto, Yu-ki Sato, Shunsaku Nakagawa, A. Yonezawa, T. Nakagawa, I. Yano, Yoshikazu Tasaki, K. Matsubara
Published 2018 · Chemistry, Medicine

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We have previously reported that oxicam-derived non-steroidal anti-inflammatory drugs (oxicam-NSAIDs), including meloxicam, piroxicam and tenoxicam, elicit protective effects against 1-methyl-4-phenyl pyridinium (MPP+)-induced cell death in a fashion independent of cyclooxygenase (COX) inhibition. We have also demonstrated that oxicam-NSAIDs suppress the decrease in phosphorylation of Akt caused by MPP+. The molecular mechanism through which oxicam-NSAIDs provide cytoprotection remains unclear. In this study, we speculated a possibility that endoplasmic reticulum (ER) stress and/or mitochondrial dysfunction, which are both causative factors of Parkinson's disease (PD), may be involved in the neuroprotective mechanism of oxicam-NSAIDs. We demonstrated here that oxicam-NSAIDs suppressed the activation of caspase-3 and cell death caused by MPP+ or ER stress-inducer, tunicamycin, in SH-SY5Y cells. Furthermore, oxicam-NSAIDs suppressed the increases in the ER stress marker CHOP (apoptosis mediator) caused by MPP+ or tunicamycin, beside suppressing eukaryotic initiation factor 2α (eIF2α) phosphorylation and the increase in ATF4 caused by MPP+. Taken together, these results suggest that oxicam-NSAIDs suppress the eIF2α-ATF4-CHOP pathway, one of the three signaling pathways in the ER stress response. Oxicam-NSAIDs suppressed the decrease in mitochondrial membrane potential depolarization caused by MPP+, indicating they also rescue cells from mitochondrial dysfunction. Akt phosphorylation levels were suppressed after the incubation with MPP+, whereas phosphorylation of eIF2α was enhanced. These results suggest that oxicam-NSAIDs prevented eIF2α phosphorylation and mitochondrial dysfunction by maintaining Akt phosphorylation (reduced by MPP+), thereby preventing cell death.
This paper references
Dementia, parkinsonism, and motor neuron disease: Neurochemical and neuropathological correlates
J. Gilbert (1988)
The Ubiquitin System
A. Hershko (1998)
Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress.
K. Haze (1999)
The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease.
P. Damier (1999)
Structure of a c-Cbl–UbcH7 Complex RING Domain Function in Ubiquitin-Protein Ligases
N. Zheng (2000)
Regulated translation initiation controls stress-induced gene expression in mammalian cells.
H. Harding (2000)
Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease.
H. Chen (2003)
Parkinsonian Mimetics Induce Aspects of Unfolded Protein Response in Death of Dopaminergic Neurons*
William A Holtz (2003)
Roles of CHOP/GADD153 in endoplasmic reticulum stress
S. Oyadomari (2004)
CHOP/GADD153 is a mediator of apoptotic death in substantia nigra dopamine neurons in an in vivo neurotoxin model of parkinsonism
Robert M. Silva (2005)
Nonsteroidal anti‐inflammatory drugs and risk of Parkinson's disease
T. Ton (2006)
ER stress and neurodegenerative diseases
D. Lindholm (2006)
Abnormal levels of prohibitin and ATP synthase in the substantia nigra and frontal cortex in Parkinson's disease
I. Ferrer (2007)
The dynamic range of transcription.
X. Darzacq (2008)
Adapting Proteostasis for Disease Intervention
W. Balch (2008)
Coupling mitochondrial dysfunction to endoplasmic reticulum stress response: a molecular mechanism leading to hepatic insulin resistance.
J. H. Lim (2009)
Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson disease and in dementia with Lewy bodies.
A. Navarro (2009)
ER stress is implicated in mitochondrial dysfunction-induced apoptosis of pancreatic beta cells
J. Lee (2010)
Meloxicam protects cell damage from 1-methyl-4-phenyl pyridinium toxicity via the phosphatidylinositol 3-kinase/Akt pathway in human dopaminergic neuroblastoma SH-SY5Y cells
Yoshikazu Tasaki (2010)
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
P. Walter (2011)
Road to Ruin: Targeting Proteins for Degradation in the Endoplasmic Reticulum
M. H. Smith (2011)
CHOP is a multifunctional transcription factor in the ER stress response.
H. Nishitoh (2012)
Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity.
Yoshikazu Tasaki (2012)
Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling in a mouse Parkinson's disease model
Yoshikazu Tasaki (2012)
Impaired mitochondrial biogenesis contributes to depletion of functional mitochondria in chronic MPP+ toxicity: dual roles for ERK1/2
J. Zhu (2012)
Endoplasmic Reticulum Stress and Parkinson's Disease: The Role of HRD1 in Averting Apoptosis in Neurodegenerative Disease
T. Omura (2013)
Mitochondrial Dysfunction in Parkinson's Disease
Hyo Eun Moon (2015)
Mitochondrial dynamics and mitochondrial quality control
H. Ni (2015)
Modulation of endoplasmic reticulum stress in Parkinson's disease.
Saori Tsujii (2015)
Cx43 Mediates Resistance against MPP+-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells via Modulating the Mitochondrial Apoptosis Pathway
In-Su Kim (2016)
Mitochondrial dysfunction in Parkinson's disease
A. Bose (2016)
ER stress and Parkinson's disease: Pathological inputs that converge into the secretory pathway
Gabriela Mercado (2016)
Resveratrol attenuates MPP+-induced mitochondrial dysfunction and cell apoptosis via AKT/GSK-3β pathway in SN4741 cells
Weijun Zeng (2017)
ER–mitochondria signaling in Parkinson’s disease
P. Gomez-Suaga (2017)

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