ABSTRACT
BACKGROUND: Impairment of mitochondrial biogenesis is associated with the pathological progression of Parkinson's disease (PD). Parkin-interacting substrate (PARIS) can be ubiquitinated by parkin and prevents the repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α). PURPOSE: This study investigated whether the neuroprotective mechanism of carnosic acid (CA) from rosemary is mediated via the regulation of PARIS and PGC-1α by parkin. METHODS: The Western blotting and RT-PCR were used to determine protein and mRNA, respectively. To investigate the protein-protein interaction of between PARIS and ubiquitin, the immunoprecipitation assay (IP assay) was utilized. Silencing of endogenous parkin or PGC-1α was performed by using transient transfection of small interfering RNA (siRNA). RESULTS: SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA) increased PARIS protein, decreased PGC-1α protein, and reduced protein and mRNA of mitochondrial biogenesis-related genes. CA pretreatment reversed the effects of 6-OHDA. By IP assay, the interaction of PARIS with ubiquitin protein caused by CA was stronger than that caused by 6-OHDA. Moreover, knockdown of parkin attenuated the ability of CA to reverse the 6-OHDA-induced increase in PARIS and decrease in PGC-1α expression. PGC-1α siRNA was used to investigate how CA influenced the effect of 6-OHDA on the modulation of mitochondrial biogenesis and apoptosis. In the presence of PGC-1α siRNA, CA could no longer significantly reverse the reduction of mitochondrial biogenesis or the induction of cleavage of apoptotic-related proteins by 6-OHDA. CONCLUSION: The cytoprotective of CA is related to the enhancement of mitochondrial biogenesis by inhibiting PARIS and inducing PGC-1α by parkin. The activation of PGC-1α-mediated mitochondrial biogenesis by CA prevents the degeneration of dopaminergic neurons, CA may have therapeutic application in PD.
Subject(s)
Abietanes/pharmacology , Mitochondria/drug effects , Neuroprotective Agents/pharmacology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Repressor Proteins/metabolism , Apoptosis/drug effects , Cell Line, Tumor , DNA-Binding Proteins/metabolism , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Humans , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Organelle Biogenesis , Oxidopamine/toxicity , Parkinson Disease/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , RNA, Small Interfering/pharmacology , Transcription Factors/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
The biological characteristics,agronomic traits,yield traits,stress resistance,quality and photosynthetic characteristics among six lily varieties were compared in order to screen out the excellent lily varieties suitable for spread planting in Hunan province. Lilium longiflorum had the longest growth period,246 days,among these six lily varieties,while others were about 170 days. The leaves of L.longiflorum,self-selected variety,L. lancifolium and L. dauricum had higher chlorophyll content. No obvious difference was found in net photosynthetic rate,stomatal conductance,transpiration rate and intercellular CO2 concentration among all varieties. The self-selected variety had the highest theoretical and actual yield,2 543. 03,1 608. 65 kg per Mu(1 Mu≈666. 7 m2),respectively,but contents of polysaccharides and flavones in bulbs were lower. All of these six lily varieties can sowing,seedling emergence,growth,flowering,mature harvest in Hunan province. L. dauricum and L. lancifolium would be provided for edible lily. L. brownie and the self-selected variety are highly susceptible varieties. L. dauricum and L. lancifolium are suitable to plant widely in disease-prone regions,due to their strong resistance. L. brownie and L. lancifolium are preferred varieties for medicinal and food using for their good quality and higher contents of polysaccharides and flavones. L. davidii had lower theoretical and actual yield,so planting extension of it should be taken into account.
Subject(s)
Lilium , Photosynthesis , Chlorophyll , Plant Leaves , Plant RootsABSTRACT
Through bioinformatics analysis, a novel lncRNA, LINC00460, was implicated in the development of multiple cancers. However, the precise expression pattern, clinical significance and biological function of LINC00460 in colorectal cancer (CRC) remain unknown. Network databases were used to investigate the correlation between LINC00460 and CRC. In situ hybridization was performed to verify the precise expression pattern and clinical significance of LINC00460 in a CRC tissue microarray, which included 92 pairs of CRC and adjacent normal tissues. The effect of LINC00460 on proliferation was evaluated by MTT, colony formation assays and flow cytometry employing SW620 and HCT116 cell lines. Cell migration and matrigel invasion assays were performed to investigate whether LINC00460 is involved in the metastasis of CRC. The expression of LINC00460 was significantly upregulated in CRC tissues and cells, associated with early stage CRC and low disease-free survival. The downregulated of LINC00460 expression increased cell proliferation by regulating the cell cycles of SW620 and HCT116 cells. LINC00460 knockdown did not affect cell migration or invasion in vitro. These findings suggest that LINC00460 may be an interesting target for the development of CRC.
