Drought is a major threat to plant growth and crop productivity. Calcium-dependent protein kinases (CDPKs, CPKs) are believed to play important roles in plant responses to drought stress. Here, we report that Arabidopsis thaliana CPK8 functions in abscisic acid (ABA)-and Ca 2+ -mediated plant responses to drought stress. The cpk8 mutant was more sensitive to drought stress than wild-type plants, while the transgenic plants overexpressing CPK8 showed enhanced tolerance to drought stress compared with wild-type plants. ABA-, H 2 O 2 -, and Ca 2+ -induced stomatal closing were impaired in cpk8 mutants. Arabidopsis CATALASE3 (CAT3) was identified as a CPK8-interacting protein, confirmed by yeast two-hybrid, coimmunoprecipitation, and bimolecular fluorescence complementation assays. CPK8 can phosphorylate CAT3 at Ser-261 and regulate its activity. Both cpk8 and cat3 plants showed lower catalase activity and higher accumulation of H 2 O 2 compared with wild-type plants. The cat3 mutant displayed a similar drought stress-sensitive phenotype as cpk8 mutant. Moreover, ABA and Ca 2+ inhibition of inward K + currents were diminished in guard cells of cpk8 and cat3 mutants. Together, these results demonstrated that CPK8 functions in ABA-mediated stomatal regulation in responses to drought stress through regulation of CAT3 activity.
Neuroinflammation has been known as an important pathogenetic contributor of Alzheimer's disease (AD). Pterostilbene is a natural compound which has neuroprotective activity. However, the effect of pterostilbene on amyloid-β (Aβ)-induced neuroinflammation has not been clarified. The aim of the present study was to investigate the effect of pterostilbene on Aβ-induced neuroinflammation in microglia. The results indicated that pterostilbene attenuated Aβ -induced cytotoxicity of BV-2 cells. Aβ induced NO production and iNOS mRNA and protein expression, while pterostilbene inhibited the induction. The expression and secretion levels of IL-6, IL-1β, and TNF-α were enhanced by Aβ treatment, whereas pterostilbene decreased them. Aβ activated NLRP3/caspase-1 inflammasome, which was inactivated by pterostilbene. In addition, the inhibitor of caspase-1 Z-YVAD-FMK attenuated the Aβ -induced neuroinflammation in BV-2 cells. In conclusion, pterostilbene attenuated the neuroinflammatory response induced by Aβ in microglia through inhibiting the NLRP3/caspase-1 inflammasome pathway, indicating that pterostilbene might be an effective therapy for AD.
Small nucleolar RNA host gene 3 (SNHG3), a long noncoding RNA (lncRNA), acts as an oncogene in hepatocellular carcinoma (HCC), whereas microRNA (miR)-326 plays an inhibitory role in some types of human cancers, including melanoma, osteosarcoma, and gastric cancer. In the present study, by analyzing 47 tissue specimens of human HCC, we found that the relative expression levels of SNHG3 were significantly higher in HCC tissues than those in the adjacent noncancerous tissues, whereas the relative expression levels of miR-326 were significantly lower in HCC tissues. Furthermore, the relative mRNA levels of Sma and Mad Related Family 3 (SMAD3) and zinc finger E-box binding homeobox 1 (ZEB1) were significantly higher in HCC tissues compared with the adjacent noncancerous tissues. In human HCC cell lines, SNHG3 overexpression promoted the proliferation, migration, and epithelial-mesenchymal transition and inhibited apoptosis, whereas knockdown of SNHG3 expression exerted the opposite effects. Importantly, miR-326 or miR-326 inhibitor restored the aforementioned effects of SNHG3 overexpression or SNHG3 knockdown. We thus found that the miR-326-response element is present in SNHG3 and the 3'-untranslated region of SMAD3 mRNA. In fact, SNHG3 overexpression increased the expression levels of SMAD3 and ZEB1, while miR-326 decreased the expression levels of SMAD3. These results suggest that SNHG3 may function as a competing endogenous RNA (ceRNA) for miR-326, which in turn enhances SMAD3 and ZEB1 expression. In conclusion, we propose that SNHG3 promotes HCC progression via the miR-326/SMAD3/ZEB1 signaling pathway. The findings may provide novel targets for the diagnosis and treatment of HCC.
Accumulation of amyloid β-peptide (Aβ) in the brain of Alzheimer disease (AD) patients is believed to be the main pathological feature of the disease. Meanwhile, miR-98-5p dysregulation was found in AD. However, whether miR-98-5p is involved in the accumulation of Aβ in AD, the underlying molecule mechanism remains unclear. In the present study, we confirmed that miR-98-5p negatively regulated sorting nexin 6 (SNX6) expression by targeting the 3'-UTR of SNX6 mRNA. Downregulation of miR-98-5p alleviated Aβ-induced viability inhibition and decreased apoptosis in SK-N-SH and SH-SY5Y cells by upregulating SNX6 expression. Furthermore, downregulation of miR-98-5p decreased SNX6-dependent levels of Aβ40, Aβ42, β-site APP-cleaving enzyme 1 (BACE1), soluble amyloid precursor protein β (sAPPβ), and membrane-associated APP β-carboxyl terminal fragment (βCTF) in SK-N-SH and HEK293 cells. Our findings demonstrate that miR-98-5p modulates SNX6 expression and thus plays a critical role in accumulation of Aβ. Therefore, miR-98-5p may be a novel therapeutic target for AD.
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