Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. Existing data suggest that early diagnosis and intervention can improve ASD outcomes. However, the causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. More mechanisms and biomarkers of autism have been found with the development of advanced technology such as mass spectrometry. Many recent studies have found a link between ASD and elevated oxidative stress, which may play a role in its development. ASD is caused by oxidative stress in several ways, including protein post-translational changes (e.g., carbonylation), abnormal metabolism (e.g., lipid peroxidation), and toxic buildup [e.g., reactive oxygen species (ROS)]. To detect elevated oxidative stress in ASD, various biomarkers have been developed and employed. This article summarizes recent studies about the mechanisms and biomarkers of oxidative stress. Potential biomarkers identified in this study could be used for early diagnosis and evaluation of ASD intervention, as well as to inform and target ASD pharmacological or nutritional treatment interventions.
Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin–Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.
Se-methylselenocysteine (SMC) is
a major selenocompound in selenium
(Se) enriched plants and has been found to ameliorate neuropathology
and cognitive deficits in triple-transgenic mice model of Alzheimer’s
disease (3 × Tg-AD mice). To explore the underlying molecular
mechanisms, the present study is designed to elucidate the protein
changes in the cortex of SMC-treated 3 × Tg-AD mice. After SMC
supplementation, proteomic analysis revealed that 181, 271, and 41
proteins were identified as differentially expressed proteins (DEPs)
between 3 × Tg-AD mice vs wild type (AD/WT group), SMC-treated
AD mice vs AD (AD + SMC/AD), and AD + SMC/WT group, respectively.
Among these, 138 proteins in the diseased group were reversed by SMC
treatment. The DEPs in AD/WT group and AD + SMC/AD group were mainly
related to metabolism, synapses, and antioxidant proteins, while their
levels were decreased in AD mice but up-regulated after treating with
SMC. In addition, we found reduced ATP levels and destroyed synaptic
structures in the AD mice brains, which were significantly ameliorated
upon SMC treatment. Our study suggests that energy metabolism disorders,
abnormal amino acid metabolism, synaptic dysfunction, and oxidative
stress may be the key pathogenic phenomena of AD. SMC reversed the
expression of proteins associated with them, which might be the main
mechanism of its intervention in AD.
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