Hydrogen sulfide is essential for Schwann cell responses to peripheral nerve injury

J Neurochem. 2015 Jan;132(2):230-42. doi: 10.1111/jnc.12932. Epub 2014 Sep 6.

Abstract

Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from substances by three enzymes: cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST). In human tissues, these enzymes are involved in tissue-specific biochemical pathways for H2 S production. For example, CBS and cysteine aminotransferase/MST are present in the brain, but CSE is not. Thus, we examined the expression of H2 S production-related enzymes in peripheral nerves. Here, we found that CSE and MST/cysteine aminotransferase, but not CBS, were present in normal peripheral nerves. In addition, injured sciatic nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration (WD); however, CSE was not up-regulated in peripheral axons. Using an ex vivo sciatic nerve explant culture, we found that the inhibition of H2 S production broadly prevented the process of nerve degeneration, including myelin fragmentation, axonal degradation, Schwann cell dedifferentiation, and Schwann cell proliferation in vitro and in vivo. Thus, these results indicate that H2 S signaling is essential for Schwann cell responses to peripheral nerve injury. Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur transferase (MST). Here, we found that CSE and MST/CAT were present in normal peripheral nerves. Injured static nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration, but CSE was not up-regulated in peripheral axons.

Keywords: Schwann cells; Wallerian degeneration; axonal degradation; cytstathionine-γ-lyase (CSE); demyelination; hydrogen sulfide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axotomy
  • Cystathionine beta-Synthase / metabolism
  • Cystathionine gamma-Lyase / metabolism
  • Cysteine / pharmacology
  • Ethylmaleimide / pharmacology
  • Hydrogen Sulfide / metabolism*
  • Hydrogen Sulfide / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organ Culture Techniques
  • Peripheral Nerve Injuries / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schwann Cells / metabolism*
  • Sciatic Nerve / injuries*
  • Sulfurtransferases / metabolism
  • Transaminases / metabolism
  • Wallerian Degeneration / metabolism*

Substances

  • Transaminases
  • cysteine aminotransferase
  • Sulfurtransferases
  • 3-mercaptopyruvate sulphurtransferase
  • Cystathionine beta-Synthase
  • Cystathionine gamma-Lyase
  • Cysteine
  • Ethylmaleimide
  • Hydrogen Sulfide