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Naroa Insausti-Urkia1,2,3,4, Estel Solsona-Vilarrasa1,2,3,4, Carmen Garcia-Ruiz1,2,3,5

  • 1Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, 08036 Barcelona, Spain.

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Sphingolipids, particularly ceramide, are vital membrane components. Neutral (NSMase) and acid (ASMase) sphingomyelinases rapidly generate ceramide, impacting liver diseases like nonalcoholic steatohepatitis.

Keywords:
acidic sphingomyelinasealcoholic and nonalcoholic steatohepatitisceramidehepatocellular carcinomaneutral sphingomyelinasesphingomyelin

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Pathology

Background:

  • Sphingolipids (SLs) are essential membrane components influencing cellular processes.
  • Ceramide, a key SL, acts as a second messenger regulating signaling pathways.
  • Ceramide is generated via de novo synthesis or sphingomyelin (SM) hydrolysis by sphingomyelinases (SMases).

Purpose of the Study:

  • To review the physiological roles of neutral (NSMase) and acid (ASMase) sphingomyelinases.
  • To explore the involvement of NSMase and ASMase in chronic and metabolic liver diseases.
  • To highlight the potential of SMase understanding for novel liver disease treatments.

Main Methods:

  • Literature review focusing on NSMase and ASMase.
  • Analysis of SMase roles in liver pathophysiology, including nonalcoholic steatohepatitis (NASH).
  • Discussion of ceramide generation mechanisms and their biological significance.

Main Results:

  • SMase-induced ceramide generation is rapid, transient, and site-specific, differing from de novo synthesis.
  • NSMase and ASMase are implicated in signaling pathways and various pathologies, notably liver diseases.
  • Nonalcoholic steatohepatitis and hepatocellular carcinoma are linked to SMase activity, exacerbated by obesity and diabetes.

Conclusions:

  • Understanding NSMase and ASMase regulation is crucial for deciphering their role in liver pathology.
  • Targeting SMases may offer new therapeutic strategies for liver diseases.
  • Further research into SMases is warranted given their association with metabolic disorders and liver cancer.