Inhibition of phosphodiesterase 4 by FCPR16 protects SH-SY5Y cells against MPP+ -induced decline of mitochondrial membrane potential and oxidative stress

Redox Biology
Jiahong ZhongHaitao Wang

Abstract

Phosphodiesterase 4 (PDE4) is a promising target for the treatment of Parkinson's disease (PD). However, the underlying mechanism has not yet been well elucidated. Additionally, most of current PDE4 inhibitors produce severe nausea and vomiting response in patients, which limit their clinical application. FCPR16 is a novel PDE4 inhibitor with little emetic potential. In the present study, the neuroprotective effect and underlying mechanism of FCPR16 against cellular apoptosis induced by 1-methyl-4-phenylpyridinium (MPP+) were examined in SH-SY5Y cells. FCPR16 (12.5-50 μM) dose-dependently reduced MPP+-induced loss of cell viability, accompanied by reductions in nuclear condensation and lactate dehydrogenase release. The level of cleaved caspase 3 and the ratio of Bax/Bcl-2 were also decreased after treatment with FCPR16 in MPP+-treated cells. Furthermore, FCPR16 (25 μM) significantly suppressed the accumulation of reactive oxygen species (ROS), prevented the decline of mitochondrial membrane potential (Δψm) and attenuated the expression of malonaldehyde level. Further studies disclosed that FCPR16 enhanced the levels of cAMP and the exchange protein directly activated by cAMP (Epac) in SH-SY5Y cells. Western blotting analysis r...Continue Reading

Citations

Jun 15, 2018·International Journal of Molecular Medicine·Yunlu JiangBo Bai
Nov 11, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Da Hye SongJeung Hee An
Dec 31, 2019·Oxidative Medicine and Cellular Longevity·Hai-Fan YuBin Guo
Sep 22, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiang SunShizhong Zhang
Feb 12, 2021·Journal of the Science of Food and Agriculture·Juan KanChangHai Jin
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ratchaneekorn ReudhabibadhPilaiwanwadee Hutamekalin
Jul 10, 2020·International Immunopharmacology·Baoyue ZhangGuanhua Du
Jul 17, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Abid BhatMeena Kishore Sakharkar
Sep 22, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yan WangXiaoqiu Liang

❮ Previous
Next ❯

Methods Mentioned

BETA
MDA
protein assay
Assay
flow cytometry
fluorescence microscopy
electrophoresis
ELISA
pharmacotherapy

Software Mentioned

Image J
GraphPad
Graphpad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.