Differentiated Astrocytes Acquire Sensitivity to Hydrogen Sulfide That Is Diminished by the Transformation into Reactive Astrocytes

Abstract

Hydrogen sulfide (H2S) enhances the induction of hippocampal long-term potentiation (LTP) and induces calcium waves in astrocytes. Based on these observations, H2S has been proposed to be a synaptic modulator in the brain. Here we show that differentiated astrocytes acquire sensitivity to H2S that is diminished by their transformation into reactive astrocytes. Although sodium hydrosulfide hydrate (NaHS), a donor of H2S, did not increase the intracellular concentration of Ca2+ in progenitors, exposure of progenitors to leukemia inhibitory factor (LIF), which induces differentiation into glial fibrillary acidic protein (GFAP)-positive astrocytes, greatly increased the sensitivity to NaHS. In contrast, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), dibutyryl cyclic AMP (db cAMP) and interleukin-1beta (IL-1beta) induced the conversion to reactive astrocytes with diminished sensitivity to NaHS. This suppressive effect of EGF on the sensitivity to NaHS was inhibited by cycloheximide, indicating that de novo protein synthesis was required for the suppression of H2S sensitivity.

Polysulfides are possible H 2 S‐derived signaling molecules in rat brain

“…During the first 10 d after preparation, astrocytes are glial fibrillary acidic protein (GFAP) negative and not sensitive to H 2 S (premature astrocytes), while after 10 d, cells become GFAP positive and sensitive to H 2 S (mature astrocytes) (6, 7). We used 6 d as premature, 19 d as mature astrocytes.…”

“…We used 6 d as premature, 19 d as mature astrocytes. When mature astrocytes are reactivated by EGF, astrocytes lost sensitivity to H 2 S (7). Because premature astrocytes or reactive astrocytes induced by EGF do not respond to H 2 S, the effect of Na 2 S 3 and Na 2 S 4 on these astrocytes was examined (7).…”

Hydrogen Sulfide Protects the Retina from Light-induced Degeneration by the Modulation of Ca2+ Influx

“…In the central nervous system, CBS is mainly localized to astrocytes, and 3MST to neurons (4,9,10). H 2 S facilitates the induction of hippocampal long-term potentiation by enhancing the activity of NMDA receptors and induces Ca 2ϩ waves in astrocytes (2,11,12). It also relaxes smooth muscle by activating K ATP channels, regulates insulin release and induces angiogenesis (3,(13)(14)(15)(16).…”

Role of Hydrogen Sulfide in Brain Synaptic Remodeling

“…Based on these observations, it could be strongly suggest that H 2 S acts as a synaptic modulator in the brain mediated through astrocytes. Tsugane, Nagai, Kimura, Oka, and Kimura (2007) showed that differentiated astrocytes acquire sensitivity to H 2 S that is diminished by their transformation into reactive astrocytes.…”