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Review
. 2023 Jun 19;39(4):549-564.
doi: 10.1007/s43188-023-00193-1. eCollection 2023 Oct.

Integrative roles of sphingosine kinase in liver pathophysiology

Kyu Min Kim  1 , Eun Jin Shin  1 , Ji Hye Yang  2 , Sung Hwan Ki  3
Affiliations
Review

Integrative roles of sphingosine kinase in liver pathophysiology

Kyu Min Kim et al. Toxicol Res. .

Abstract

Bioactive sphingolipids and enzymes that metabolize sphingolipid-related substances have been considered as critical messengers in various signaling pathways. One such enzyme is the crucial lipid kinase, sphingosine kinase (SphK), which mediates the conversion of sphingosine to the potent signaling substance, sphingosine-1-phosphate. Several studies have demonstrated that SphK metabolism is strictly regulated to maintain the homeostatic balance of cells. Here, we summarize the role of SphK in the course of liver disease and illustrate its effects on both physiological and pathological conditions of the liver. SphK has been implicated in a variety of liver diseases, such as steatosis, liver fibrosis, hepatocellular carcinoma, and hepatic failure. This study may advance the understanding of the cellular and molecular foundations of liver disease and establish therapeutic approaches via SphK modulation.

Keywords: Liver; Sphingolipids; Sphingosine kinase.

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Conflict of interest statement

Conflict of interestThe authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Metabolism of Sphingolipids. Three major pathways are illustrated; de novo synthesis, the hydrolytic pathway, and the salvage pathway. (1) De novo synthesis pathway is the ceramide synthesis in the endoplasmic reticulum where the ceramide is carried to the Golgi bodies via ceramide transport protein 1 (CERT1) and exerts as a substrate for the sphingomyelin and complex glycosphingolipids. Complex glycosphingolipids and sphingomyelin are carried to the plasma membrane via vesicular transport. (2) Hydrolytic pathway acts as a generator of ceramide by neutral or acidic sphingomyelinase (SMase) in the plasma membrane. (3) In the salvage pathway, sphingosine released from the lysosome converts to ceramide by ceramide synthase (CERS). (ACER neutral ceramidase in Golgi bodies, ASAH acidic ceramidase in lysosomes, CERK Ceramide kinase, CPP Ceramide-1-phosphate phosphatase, SMS Sphingomyelin synthase, SphK Sphingosine kinase, SPL S1P lyase, SPP Sphingosine-1-phosphate phosphatase, SPT Serine palmitoyltransferase)
Fig. 2
Fig. 2
Regulatory mechanism of SphK. Transcription factors and post-transcriptional mechanisms (microRNA, phosphorylation, and acetylation) involved in SphK regulation are demonstrated. Factors related to SphK1 and SphK2 are listed in red and blue, respectively
Fig. 3
Fig. 3
Roles of SphK in liver diseases. SphK is interactively mediated in liver pathophysiology. However, an obvious understanding of the control of SphK in liver disease remains to be accomplished
See this image and copyright information in PMC

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