scholarly journals Liver Sphingomyelin Synthase 1 Deficiency Causes Steatosis, Steatohepatitis, Fibrosis and Tumorigenesis: An Effect of Glucosylceramide Accumulation

iScience ◽  
2021 ◽  
pp. 103449
Author(s):  
Zhiqiang Li ◽  
Yeun-po Chiang ◽  
Mulin He ◽  
Tilla S. Worgall ◽  
Hongwen Zhou ◽  
...  
Keyword(s):  
Sphingomyelin Synthase

Pathogenic and Compensatory Mechanisms in Epidermis of Sphingomyelin Synthase 2-Deficient Mice

2021 ◽  
pp. 1-7
Author(s):  
Shota Sakai ◽  
Asami Makino ◽  
Akihito Nishi ◽  
Takeshi Ichikawa ◽  
Tadashi Yamashita ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Lamellar Body ◽  
Lipid Mediator ◽  
Permeability Barrier ◽  
Compensatory Mechanisms ◽  
Terrestrial Environment ◽  
Sphingomyelin Synthase ◽  
Epidermal Permeability Barrier ◽  
Deficient Mice

Sphingomyelin (SM) is a constituent of cellular membranes, while ceramides (Cer) produced from SM on plasma membranes serve as a lipid mediator that regulates cell proliferation, differentiation, and apoptosis. In the skin, SM also is a precursor of Cer, an important constituent of epidermal permeability barrier. We investigated the role of epidermal SM synthase (SMS)2, an isoform of SMS, which modulates SM and Cer levels on plasma membranes. Although SMS2-knockout (SMS2-KO) mice were not neonatal lethal, an ichthyotic phenotype with epidermal hyperplasia and hyperkeratosis was evident at birth, which persisted until 2 weeks of age. These mice showed abnormal lamellar body morphology and secretion, and abnormal extracellular lamellar membranes in the stratum corneum. These abnormalities were no longer evident by 4 weeks of age in SMS2-KO mice. Our study suggests that (1) exposure to a dry terrestrial environment initiates compensatory responses, thereby normalizing epidermal ichthyotic abnormalities and (2) that a nonlethal gene abnormality can cause an ichthyotic skin phenotype.

Sphingomyelin synthase knockout mice exhibit an ichthyotic phenotype with epidermal lipid abnormalities

2016 ◽  
Vol 84 (1) ◽  
pp. e129
Author(s):  
Akihito Nishi ◽  
Takeshi Ichikawa ◽  
Shota Sakai ◽  
Tadashi Yamashita ◽  
Yoshihiro Tokudome ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Sphingomyelin Synthase ◽  
Lipid Abnormalities

scholarly journals Sphingomyelin Synthase 2 Activity and Liver Steatosis

2013 ◽  
Vol 33 (7) ◽  
pp. 1513-1520 ◽  
Author(s):  
Yue Li ◽  
Jibin Dong ◽  
Tingbo Ding ◽  
Ming-Shang Kuo ◽  
Guoqing Cao ◽  
...  
Keyword(s):  
Liver Steatosis ◽  
Sphingomyelin Synthase

scholarly journals A Genome-Wide CRISPR/Cas9 Screen Reveals the Requirement of Host Sphingomyelin Synthase 1 for Infection with Pseudorabies Virus Mutant gD–Pass

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1574
Author(s):  
Julia E. Hölper ◽  
Finn Grey ◽  
John Kenneth Baillie ◽  
Tim Regan ◽  
Nicholas J. Parkinson ◽  
...  
Keyword(s):  
Pseudorabies Virus ◽  
Resistant Cell ◽  
Dna Viruses ◽  
Sphingomyelin Synthase ◽  
Host Cell Proteins ◽  
Genome Wide ◽  
A Genome ◽  
Efficient Replication ◽  
Exogenous Expression ◽  
Virus Mutant

Herpesviruses are large DNA viruses, which encode up to 300 different proteins including enzymes enabling efficient replication. Nevertheless, they depend on a multitude of host cell proteins for successful propagation. To uncover cellular host factors important for replication of pseudorabies virus (PrV), an alphaherpesvirus of swine, we performed an unbiased genome-wide CRISPR/Cas9 forward screen. To this end, a porcine CRISPR-knockout sgRNA library (SsCRISPRko.v1) targeting 20,598 genes was generated and used to transduce porcine kidney cells. Cells were then infected with either wildtype PrV (PrV-Ka) or a PrV mutant (PrV-gD–Pass) lacking the receptor-binding protein gD, which regained infectivity after serial passaging in cell culture. While no cells survived infection with PrV-Ka, resistant cell colonies were observed after infection with PrV-gD–Pass. In these cells, sphingomyelin synthase 1 (SMS1) was identified as the top hit candidate. Infection efficiency was reduced by up to 90% for PrV-gD–Pass in rabbit RK13-sgms1KO cells compared to wildtype cells accompanied by lower viral progeny titers. Exogenous expression of SMS1 partly reverted the entry defect of PrV-gD–Pass. In contrast, infectivity of PrV-Ka was reduced by 50% on the knockout cells, which could not be restored by exogenous expression of SMS1. These data suggest that SMS1 plays a pivotal role for PrV infection, when the gD-mediated entry pathway is blocked.

scholarly journals Sphingomyelin synthase 1 activity is regulated by theBCR-ABLoncogene

2012 ◽  
Vol 54 (3) ◽  
pp. 794-805 ◽  
Author(s):  
Tara Ann Burns ◽  
Marimuthu Subathra ◽  
Paola Signorelli ◽  
Young Choi ◽  
Xiaofeng Yang ◽  
...  
Keyword(s):  
Sphingomyelin Synthase

Multi-step splicing of sphingomyelin synthase linear and circular RNAs

Gene ◽  
2018 ◽  
Vol 654 ◽  
pp. 14-22 ◽  
Author(s):  
Ivan B. Filippenkov ◽  
Olga Yu. Sudarkina ◽  
Svetlana A. Limborska ◽  
Lyudmila V. Dergunova
Keyword(s):  
Circular Rnas ◽  
Sphingomyelin Synthase

scholarly journals Knockdown of sphingomyelin synthase 2 inhibits osteoclastogenesis by decreasing RANKL expression in mouse primary osteoblasts

2019 ◽  
Vol 40 (5) ◽  
pp. 189-196 ◽  
Author(s):  
Yoshihiro YOSHIKAWA ◽  
Tatsuya YOSHIZAWA ◽  
Eisuke DOMAE ◽  
Yuya HIRAI ◽  
Aiko KAMADA ◽  
...  
Keyword(s):  
Rankl Expression ◽  
Sphingomyelin Synthase ◽  
Primary Osteoblasts

scholarly journals Sphingomyelin Synthase 2 Participate in the Regulation of Sperm Motility and Apoptosis

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4231
Author(s):  
Xiatian Li ◽  
Tao Luo ◽  
Hua Li ◽  
Nianlong Yan
Keyword(s):  
Signaling Pathways ◽  
Sperm Motility ◽  
Acrosome Reaction ◽  
Caspase 3 ◽  
Human Sperm ◽  
Erk Signaling ◽  
Sperm Function ◽  
Sphingomyelin Synthase ◽  
Protein Levels ◽  
Penetration Ability

Sphingomylin participates in sperm function in animals, and also regulates the Akt and ERK signaling pathways, both of which are associated with the asthenospermia. Sphingomyelin synthase 2 (SMS2) is involved in the biosynthesis of sphingomylin. To determine the relationship between SMS2 and human sperm function, we analyzed the distribution of SMS2 in human sperm and testes, and SMS2 expression in patients with asthenospermia and normozoospermia; human sperm were treated with anti-SMS2, and the sperm motility, penetration ability into methylcellulose, capacitation and acrosome reaction, and sperm [Ca2+]i imaging were evaluated, while the Akt and ERK pathway and cleaved caspase 3 were also analyzed. Results showed that SMS2 was localized in the testis and human sperm, and the protein levels of normozoospermia were higher than asthenospermia. Inhibition of SMS2 activity significantly decreased sperm motility and penetration ability into methylcellulose, but had no influence on capacitation and acrosome reaction, or on intracellular [Ca2+]i compared to IgG-treated control groups. Moreover, the phosphorylation level of Akt was decreased, whereas the phosphorylation of ERK and cleaved-caspase 3 levels were significantly increased. Taken together, SMS2 can affect sperm motility and penetration ability into methylcellulose, and participate in apoptosis associated with the Akt and ERK signaling pathways.

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