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Peroxiredoxin II Maintains the Mitochondrial Membrane Potential against Alcohol-Induced Apoptosis in HT22 Cells.

ABSTRACT: Excessive alcohol intake can significantly reduce cognitive function and cause irreversible learning and memory disorders. The brain is particularly vulnerable to alcohol-induced ROS damage; the hippocampus is one of the most sensitive areas of the brain for alcohol neurotoxicity. In the present study, we observed significant increasing of intracellular ROS accumulations in Peroxiredoxin II (Prx II) knockdown HT22 cells, which were induced by alcohol treatments. We also found that the level of ROS in mitochondrial was also increased, resulting in a decrease in the mitochondrial membrane potential. The phosphorylation of GSK3? (Ser9) and anti-apoptotic protein Bcl2 expression levels were significantly downregulated in Prx II knockdown HT22 cells, which suggests that Prx II knockdown HT22 cells were more susceptible to alcohol-induced apoptosis. Scavenging the alcohol-induced ROS with NAC significantly decreased the intracellular ROS levels, as well as the phosphorylation level of GSK3? in Prx II knockdown HT22 cells. Moreover, NAC treatment also dramatically restored the mitochondrial membrane potential and the cellular apoptosis in Prx II knockdown HT22 cells. Our findings suggest that Prx II plays a crucial role in alcohol-induced neuronal cell apoptosis by regulating the cellular ROS levels, especially through regulating the ROS-dependent mitochondrial membrane potential. Consequently, Prx II may be a therapeutic target molecule for alcohol-induced neuronal cell death, which is closely related to ROS-dependent mitochondria dysfunction.

SUBMITTER: Jin MH

PROVIDER: S-EPMC7023630 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Peroxiredoxin II Maintains the Mitochondrial Membrane Potential against Alcohol-Induced Apoptosis in HT22 Cells.

Jin Mei-Hua MH Yu Jia-Bin JB Sun Hu-Nan HN Jin Ying-Hua YH Shen Gui-Nan GN Jin Cheng-Hao CH Cui Yu-Dong YD Lee Dong-Seok DS Kim Sun-Uk SU Kim Ji-Su JS Kwon Taeho T Han Ying-Hao YH

Antioxidants (Basel, Switzerland) 20191218 1

Excessive alcohol intake can significantly reduce cognitive function and cause irreversible learning and memory disorders. The brain is particularly vulnerable to alcohol-induced ROS damage; the hippocampus is one of the most sensitive areas of the brain for alcohol neurotoxicity. In the present study, we observed significant increasing of intracellular ROS accumulations in Peroxiredoxin II (Prx II) knockdown HT22 cells, which were induced by alcohol treatments. We also found that the level of R ...[more]

PMID: 31861323

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Project description:Phytic acid (PA) has been reported to possess anti-inflammatory and antioxidant properties that are critical for neuroprotection in neuronal disorders. This raises the question of whether PA can effectively protect sensory neurons against chemotherapy-induced peripheral neuropathy (CIPN). Peripheral neuropathy is a dose-limiting side effect of chemotherapy treatment often characterized by severe and abnormal pain in hands and feet resulting from peripheral nerve degeneration. Currently, there are no effective treatments available that can prevent or cure peripheral neuropathies other than symptomatic management. Herein, we aim to demonstrate the neuroprotective effects of PA against the neurodegeneration induced by the chemotherapeutics cisplatin (CDDP) and oxaliplatin. Further aims of this study are to provide the proposed mechanism of PA-mediated neuroprotection. The neuronal protection and survivability against CDDP were characterized by axon length measurements and cell body counting of the dorsal root ganglia (DRG) neurons. A cellular phenotype study was conducted microscopically. Intracellular reactive oxygen species (ROS) was estimated by fluorogenic probe dichlorofluorescein. Likewise, mitochondrial membrane potential (MMP) was assessed by fluorescent MitoTracker Orange CMTMRos. Similarly, the mitochondria-localized superoxide anion radical in response to CDDP with and without PA was evaluated. The culture of primary DRG neurons with CDDP reduced axon length and overall neuronal survival. However, cotreatment with PA demonstrated that axons were completely protected and showed increased stability up to the 45-day test duration, which is comparable to samples treated with PA alone and control. Notably, PA treatment scavenged the mitochondria-specific superoxide radicals and overall intracellular ROS that were largely induced by CDDP and simultaneously restored MMP. These results are credited to the underlying neuroprotection of PA in a platinum-treated condition. The results also exhibited that PA had a synergistic anticancer effect with CDDP in ovarian cancer in vitro models. For the first time, PA's potency against CDDP-induced PN is demonstrated systematically. The overall findings of this study suggest the application of PA in CIPN prevention and therapeutic purposes.

Project description:BACKGROUND:Mounting evidence shows that ROS regulation by various antioxidants is essential for the expression of enzymes involved in steroidogenesis and maintenance of progesterone production by the corpus luteum (CL). However, the underlying mechanisms of peroxiredoxin 1 (PRDX1), an antioxidant enzyme, in luteal function for progesterone production in mice have not been reported. The aim of this study was to evaluate the functional link between PRDX1 and progesterone production in the CL of Prdx1 knockout (K/O) mice in the functional stage of CL. METHODS:The expression pattern of the unfolded protein response (UPR) signaling pathways, endoplasmic reticulum (ER) stress-induced apoptosis related genes and peroxiredoxins 1 (PRDX1) were investigated by western blotting analysis in CL tissue of 10 weeks mice during functional stage of CL. The protein levels of these genes after ER-stress inducer tunicamycin (Tm), ER-stress inhibitor tauroursodeoxycholic acid (TUDCA) and ROS scavenger, N-acetylcysteine (NAC) stimulation by intraperitoneal (i.p) injection were also investigated in CL tissue of wild type (WT) mice. Finally, we examined progesterone production and UPR signaling related gene expression in CL tissue of Prdx1 K/O mice. RESULTS:We demonstrated that PRDX1 deficiency in the functional stage activates the UPR signaling pathways in response to ER stress-induced apoptosis. Interestingly, CL number, serum progesterone levels, and steroidogenic enzyme expression in Prdx1 K/O mice decreased significantly, compared to those in wild type mice. Levels of UPR signaling pathway markers (GRP78/BIP, P50ATF6, and phosphorylated (p)-eIF2) and ER-stress associated apoptotic factors (CHOP, p-JNK, and cleaved caspase-3) were dramatically increased in the CL tissue of Prdx1 K/O mice. In addition, administration of the NAC, reduced progesterone production and activated ER-stress-induced UPR signaling in the CL tissue obtained from the ovary of Prdx1 K/O mice. Taken together, these results indicated that reduction in serum progesterone levels and activation of ER-stress-induced UPR signaling are restored by NAC injection in the CL of Prdx1 K/O mice. CONCLUSION:These observations provide the first evidence regarding the basic mechanisms connecting PRDX1 and progesterone production in the functional stage of CL.

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Peroxiredoxin II Maintains the Mitochondrial Membrane Potential against Alcohol-Induced Apoptosis in HT22 Cells.

Publications

Peroxiredoxin II Maintains the Mitochondrial Membrane Potential against Alcohol-Induced Apoptosis in HT22 Cells.

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