The unfolded protein response (UPR) is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. However, tumor-specific UPR transducers are largely unknown. In the present study, we identified CD147, a cancer biomarker, as an UPR inducer in hepatocellular carcinoma (HCC). The expression of the major UPR target, Bip, was found to be positively associated with CD147 in human hepatoma tissues. By phosphorylating FAK and Src, CD147-enhanced TFII-I tyrosine phosphorylation at Tyr248. CD147 also induced p-TFII-I nuclear localization and binding to the Bip promoter where endoplasmic reticulum (ER) stress response element 1 (ERSE1) ( À 82/ À 50) is the most efficient target of the three ERSEs, thus increasing transcription of Bip. Furthermore, by inducing UPR, CD147 inhibited HCC cell apoptosis and decreased cell Adriamycin chemosensitivity, thus decreasing the survival rate of hepatoma-bearing nude mice. Together, these results reveal pivotal roles for CD147 in modulating the UPR in HCC and raise the possibility that CD147 is a target that promotes HCC cell apoptosis and increases the sensitivity of tumors to anti-cancer drugs. Therefore, CD147 inhibition provides an opportunity to enhance the efficacy of existing agents and represents a novel target for HCC treatment. The uncontrolled growth and insufficient vascularization of a tumor mass lead to a stressed state in the tumor microenvironment, which includes low oxygen supply, nutrient deprivation and pH changes. Microenvironment stresses directly impinge on the luminal milieu of the endoplasmic reticulum (ER) and might be sufficiently severe to cause ER stress (ERS). 1 These ERS conditions activate a range of cellular stress response pathways, including the unfolded protein response (UPR). 2,3 UPR activation has profound consequences for tumor growth and resistance to radiotherapy and chemotherapy. [4][5][6] Therefore, the UPR might be responsible for the failure of some patients to respond to treatment and is associated with a poor prognosis. 7 Given the observation that UPR is correlated with certain types of aggressive tumors, drug resistance, recurrence and poor survival, 8-11 the inhibition of the UPR pathway may yield more efficient treatments for cancer.Although there is sufficient evidence to indicate that the UPR is generally activated in solid tumors, the UPR remains poorly characterized in cancers. The three major UPR transducers are inositol-requiring enzyme 1 (IRE1), pancreatic kinase-like ER kinase (PERK) and the UPR-specific transcription factor, activating transcription factor 6 (ATF6).These factors all sense the presence of unfolded proteins in the ER lumen and transduce signals to the nucleus that activate the transcription of UPR target genes, such as Bip (also called glucose-regulated protein 78). 12-14 The overexpression of Bip as a result of the three major transducers has been reported in malignant breast disease, colon cancer and gastric and esophageal adenocarcinomas. [15][16][17][18] It has also been...

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Study design: Observational cross-section study. Objective: The objective of our study was to determine if phosphorylation of aggregated neurofilaments (NFs) would occur in autoimmune-mediated motor neuron injury. Our main hypothesis was that autoimmune-mediated damage of spinal cord motor neurons may influence NF phosphorylation and lead to NF aggregation. Methods: A total of 20 guinea pigs were inoculated with bovine spinal cord anterior horn homogenates (experimental autoimmune gray matter model) and 20 guinea pigs were inoculated with phosphate-buffered saline (control). NF phosphorylation and aggregation were observed by immunohistochemistry and electron microscopic examination. Data were analyzed using Student's t-test with Po0.05 being considered significant. Results: Abnormal phosphorylation and distribution of NF occurred in motor neurons and axons of animals with experimental autoimmune gray matter disease but not in the control animals. Conclusion: Aberrant accumulation and phosphorylation of neurofilaments in perikarya of spinal cord motor neurons occur in immune-mediated motor neuron death. As both immunologic response and alteration of neurofilaments are observed in amyotrophic lateral sclerosis (ALS) patients and aberrant neurofilament change harms motor neurons, our present findings suggest that autoimmunity-induced ALS may mediate in part through neurofilament modification.

ABSTRACT. Potassium is one of the three main mineral nutrients, and is vital for leaf growth and the quality of tobacco (Nicotiana tabacum) plants. In recent years, the isobaric tags for relative and absolute quantitation (iTRAQ) method has been one of the most popular techniques for quantitative proteomic analysis. In this study, we used iTRAQ to compare protein abundances in the roots of control and low potassium-treated tobacco seedlings, and found that 108 proteins were differentially expressed between the two treatments. Of these, 34 were upregulated and 74 were downregulated, and 39 (36%) were in the chloroplasts. Kyoto Encyclopedia of Genes and Genomes pathway enrichment results suggested that metabolic pathways were the dominant pathways (10 upregulated and 14 downregulated proteins). Ten proteins involved in the pyruvate metabolism pathway increased their expression levels, and 17 upregulated proteins were enriched in the ribosomes category. To evaluate correlations between protein and gene transcript abundances, the expression patterns of 12 randomly chosen genes were examined. A quantitative real-time polymerase chain reaction revealed that the 12 genes were induced after low potassium treatment for 3, 6, 12, and 24 h. Our results demonstrate that low potassium levels affect protein profiles in tobacco roots.