Myeloid-associated lipin-1 transcriptional co-regulatory activity is atheroprotective

Author(s):  
Cassidy M.R. Blackburn ◽  
Robert M. Schilke ◽  
Aimee E. Vozenilek ◽  
Sunitha Chandran ◽  
Temitayo T. Bamgbose ◽  
...  
Keyword(s):  
Author(s):  
Cassidy M.R. Blackburn ◽  
Robert M. Schilke ◽  
Aimee E. Vozenilek ◽  
Brian N. Finck ◽  
Matthew D. Woolard

AbstractDuring atherosclerosis, macrophages engulf and break down deposited modified low-density lipoproteins (modLDLs) into lipids and free fatty acids. The lipids and free fatty acids from these modLDLs either need to be stored during a process called glycerolipid synthesis or broken down during β-oxidation. In addition, free fatty acids can activate transcription factors to promote a pro-resolving macrophage phenotype. The protein lipin-1 is involved in both glycerolipid synthesis and β-oxidation. Lipin-1 enzymatic activity is a key step in the glycerolipid synthesis pathway; lipin-1 transcriptional co-regulatory activity either augments or represses various transcription factors that are activated via free fatty acids that promote β-oxidation and inhibit inflammation. Lipin-1 enzymatic activity increases pro-inflammatory macrophage phenotypes and is atherogenic. In contrast, we have also demonstrated that lipin-1 transcriptional co-regulatory activity promotes pro-resolving macrophage phenotypes leading us to the hypothesis that lipin-1 transcriptional co-regulatory activity is atheroprotective. Using a mouse model to delete lipin-1 in myeloid cells, we have demonstrated that loss of lipin-1 increases plaque size and pro-inflammatory gene expression. We have also shown mice lacking lipin-1 in myeloid cells have increased plaque collagen deposition and larger necrotic core formation. Combined, these data suggest that though lipin-1 enzymatic activity is atherogenic, lipin-1 transcriptional co-regulatory activity is atheroprotective. Overall, the results suggest that the dual activities of lipin-1 contribute to atherosclerosis progression in opposite ways.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Dan Hou ◽  
Ling Li ◽  
Tengfei Ma ◽  
Jialong Pei ◽  
Zhongyu Zhao ◽  
...  

AbstractBamboo is known for its edible shoots and beautiful texture and has considerable economic and ornamental value. Unique among traditional flowering plants, many bamboo plants undergo extensive synchronized flowering followed by large-scale death, seriously affecting the productivity and application of bamboo forests. To date, the molecular mechanism of bamboo flowering characteristics has remained unknown. In this study, a SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1)-like gene, BoMADS50, was identified from Bambusa oldhamii. BoMADS50 was highly expressed in mature leaves and the floral primordium formation period during B. oldhamii flowering and overexpression of BoMADS50 caused early flowering in transgenic rice. Moreover, BoMADS50 could interact with APETALA1/FRUITFULL (AP1/FUL)-like proteins (BoMADS14-1/2, BoMADS15-1/2) in vivo, and the expression of BoMADS50 was significantly promoted by BoMADS14-1, further indicating a synergistic effect between BoMADS50 and BoAP1/FUL-like proteins in regulating B. oldhamii flowering. We also identified four additional transcripts of BoMADS50 (BoMADS50-1/2/3/4) with different nucleotide variations. Although the protein-CDS were polymorphic, they had flowering activation functions similar to those of BoMADS50. Yeast one-hybrid and transient expression assays subsequently showed that both BoMADS50 and BoMADS50-1 bind to the promoter fragment of itself and the SHORT VEGETATIVE PHASE (SVP)-like gene BoSVP, but only BoMADS50-1 can positively induce their transcription. Therefore, nucleotide variations likely endow BoMADS50-1 with strong regulatory activity. Thus, BoMADS50 and BoMADS50-1/2/3/4 are probably important positive flowering regulators in B. oldhamii. Moreover, the functional conservatism and specificity of BoMADS50 and BoMADS50-1 might be related to the synchronized and sporadic flowering characteristics of B. oldhamii.


2011 ◽  
Vol 28 (1) ◽  
pp. 142-144 ◽  
Author(s):  
E. Dassi ◽  
A. Malossini ◽  
A. Re ◽  
T. Mazza ◽  
T. Tebaldi ◽  
...  
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