sepiapterin reductase
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2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Wang ◽  
Qin Zheng ◽  
Chen Yu ◽  
Changkun Pan ◽  
Peng Luo ◽  
...  

Sepiapterin reductase (Spr) plays an essential role in the biosynthesis of tetrahydrobiopterin (BH4), a key cofactor of multiple enzymes involved in various physiological and immune processes. Suppression of Spr could result in BH4 deficiency-caused diseases in human and murine models. However, information on the biological function of Spr in invertebrates is limited. In this study, two Sprs (CG12116 and Sptr) from Drosophila melanogaster were found to be downregulated in transgenic flies overexpressing white spot syndrome virus (WSSV) immediate-early protein WSV056. CG12116 and Sptr exerted an inhibitory effect on the replication of the Drosophila C virus. A Litopenaeus vannamei Spr (LvSpr) exhibiting similarity of 64.1–67.5% and 57.3–62.2% to that of invertebrate and vertebrate Sprs, respectively, were cloned. L. vannamei challenged with WSSV revealed a significant decrease in LvSpr transcription and Spr activity in hemocytes. In addition, the BH4 co-factored nitric oxide synthase (Nos) activity in shrimp hemocytes was reduced in WSSV-infected and LvSpr knockdown shrimp, suggesting WSSV probably inhibits the LvNos activity through LvSpr downregulation to limit the production of nitric oxide (NO). Knockdown of LvSpr and LvNos caused the reduction in NO level in hemocytes and the increase of viral copy numbers in WSSV-infected shrimp. Supplementation of NO donor DETA/NO or double gene knockdown of WSV056 + LvSpr and WSV056 + LvNos recovered the NO production, whereas the WSSV copy numbers were decreased. Altogether, the findings demonstrated that LvSpr and LvNos could potentially inhibit WSSV. In turn, the virus has evolved to attenuate NO production via LvSpr suppression by WSV056, allowing evasion of host antiviral response to ensure efficient replication.


2020 ◽  
Vol 24 (17) ◽  
pp. 9495-9506
Author(s):  
Yao Wu ◽  
Peng Chen ◽  
Li Sun ◽  
Shengtao Yuan ◽  
Zujue Cheng ◽  
...  

Neurology ◽  
2020 ◽  
Vol 95 (3) ◽  
pp. e332-e334
Author(s):  
Tina Mainka ◽  
Jessica Hoffmann ◽  
Andrea A. Kühn ◽  
Saskia Biskup ◽  
Christos Ganos

2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Yao Wu ◽  
Hongzhi Du ◽  
Meixiao Zhan ◽  
Hongxv Wang ◽  
Peng Chen ◽  
...  

2020 ◽  
Vol 7 (3) ◽  
pp. 191888
Author(s):  
Guihua Jiang ◽  
Jiangbo Song ◽  
Hai Hu ◽  
Xiaoling Tong ◽  
Fangyin Dai

Human sepiapterin reductase (SR) deficiency is an inherited disease caused by SPR gene mutations and is a monoamine neurotransmitter disorder. Here, we investigated whether the silkworm lemon mutant could serve as a model of SR deficiency. A point mutation in the BmSPR gene led to a five amino acid deletion at the carboxyl terminus in the lemon mutant. In addition, classical phenotypes seen in SR deficient patients were observed in the lemon mutant, including a normal phenylalanine level, a decreased dopamine and serotonin content, and an increased neopterin level. A recovery test showed that the replenishment of l -dopa significantly increased the dopamine level in the lemon mutant. The silkworm lemon mutant also showed negative behavioural abilities. These results suggest that the silkworm lemon mutant has an appropriate genetic basis and meets the biochemical requirements to be a model of SR deficiency. Thus, the silkworm lemon mutant can serve as a candidate animal model of SR deficiency, which may be helpful in facilitating accurate diagnosis and effective treatment options of SR deficiency.


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