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Interaction of H2S with Calcium Permeable Channels and Transporters.

Zhang W, Xu C, Yang G, Wu L, Wang R - Oxid Med Cell Longev (2015)

Bottom Line: More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration.However, the understanding of the molecular targets and mechanisms is incomplete.Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, Heilongjiang 150086, China.

ABSTRACT
A growing amount of evidence has suggested that hydrogen sulfide (H2S), as a gasotransmitter, is involved in intensive physiological and pathological processes. More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration. These groups have demonstrated the reciprocal interaction between H2S and calcium ion channels and transporters, such as L-type calcium channels (LTCC), T-type calcium channels (TTCC), sodium/calcium exchangers (NCX), transient receptor potential (TRP) channels, β-adrenergic receptors, and N-methyl-D-aspartate receptors (NMDAR) in different cells. However, the understanding of the molecular targets and mechanisms is incomplete. Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions. In this review, we elucidate that H2S controls intracellular calcium homeostasis and the underlying mechanisms.

No MeSH data available.


Related in: MedlinePlus

Hydrogen sulfide regulating L-type calcium channels by S-sulfhydration. LTCC consists of a pore-forming α subunit which contains four homologous domains (I–IV), each with six transmembrane segments (S1–S6). The S1–S4 segments are the voltage sensor, and the S5-S6 segments form the channel pore and selectivity filter. The cartoon demonstrated that H2S modifies the –SH from sulfhydryl donor which is transformed to free cysteine sulfhydryl and forms covalent persulfide (–SSH).
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fig1: Hydrogen sulfide regulating L-type calcium channels by S-sulfhydration. LTCC consists of a pore-forming α subunit which contains four homologous domains (I–IV), each with six transmembrane segments (S1–S6). The S1–S4 segments are the voltage sensor, and the S5-S6 segments form the channel pore and selectivity filter. The cartoon demonstrated that H2S modifies the –SH from sulfhydryl donor which is transformed to free cysteine sulfhydryl and forms covalent persulfide (–SSH).

Mentions: LTCCs are integral in excitation/contraction coupling and are one of the main channels for extracellular Ca2+ influx in myocardial cells. In 2002, Zhao and Wang first reported that H2S could directly inhibit calcium influx from LTCCs in smooth-muscle cells [21]. Moreover, in 2009, Sun et al. further demonstrated that H2S, as a novel inhibitor of LTCC, has negative inotropic effects in rat cardiomyocytes [22]. In a recent study, Avanzato et al. investigated the role of H2S in regulating VDCCs and the related functional effects on the cardiomyoblast cell line H9c2. They found that H2S inhibits LTCCs and TTCCs in H9c2. Pretreatment with NaHS (a donor of H2S) prevented cell death via H2O2 through inhibiting LTCCs. Their results were the first to demonstrate that H2S protects rat cardiomyoblasts against oxidative stress through inhibition of LTCCs [23]. In addition, Tang et al. suggested that exogenous and endogenous H2S inhibited pancreatic insulin secretion by inhibiting LTCCs activity. They confirmed that NaHS reversibly decreased LTCC current density in a concentration-dependent manner in CSE WT pancreatic beta cells. Furthermore, they observed that DL-propargylglycine (an inhibitor of CSE) increased the basal LTCC activity in beta cells from CSE WT mice, but not in pancreatic beta cells from CSE-KO mice. Pancreatic beta cells from CSE-KO mice displayed a higher LTCCs density than those from WT mice. These results suggested that a novel mechanism for regulating insulin secretion was related to the CSE/H2S system, which controlled LTCC activity [24]. Recently, some data showed that exogenous and endogenous H2S can modify cystein residues of different proteins through S-sulfhydration. The –SH from sulfhydryl donor is transformed to free cysteine sulfhydryl and forms covalent persulfide (–SSH) [25, 26]. In 2012, Zhang and his coworkers showed that NaHS inhibited the peak amplitude of the L-type calcium current in a concentration-dependent manner and could be partly inhibited by the oxidant sulfhydryl modifier diamide (DM). They explained that dithiothreitol (DTT), a reductant that transforms disulfide bridges into sulfhydryl groups in cysteine-containing proteins, could significantly reverse NaHS-induced inhibition of calcium current from LTCCs. Their results suggested that H2S inhibited L-type calcium currents depending on the sulfhydryl group in rat cardiomyocytes [27] (Figure 1).


Interaction of H2S with Calcium Permeable Channels and Transporters.

Zhang W, Xu C, Yang G, Wu L, Wang R - Oxid Med Cell Longev (2015)

Hydrogen sulfide regulating L-type calcium channels by S-sulfhydration. LTCC consists of a pore-forming α subunit which contains four homologous domains (I–IV), each with six transmembrane segments (S1–S6). The S1–S4 segments are the voltage sensor, and the S5-S6 segments form the channel pore and selectivity filter. The cartoon demonstrated that H2S modifies the –SH from sulfhydryl donor which is transformed to free cysteine sulfhydryl and forms covalent persulfide (–SSH).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4442308&req=5

fig1: Hydrogen sulfide regulating L-type calcium channels by S-sulfhydration. LTCC consists of a pore-forming α subunit which contains four homologous domains (I–IV), each with six transmembrane segments (S1–S6). The S1–S4 segments are the voltage sensor, and the S5-S6 segments form the channel pore and selectivity filter. The cartoon demonstrated that H2S modifies the –SH from sulfhydryl donor which is transformed to free cysteine sulfhydryl and forms covalent persulfide (–SSH).
Mentions: LTCCs are integral in excitation/contraction coupling and are one of the main channels for extracellular Ca2+ influx in myocardial cells. In 2002, Zhao and Wang first reported that H2S could directly inhibit calcium influx from LTCCs in smooth-muscle cells [21]. Moreover, in 2009, Sun et al. further demonstrated that H2S, as a novel inhibitor of LTCC, has negative inotropic effects in rat cardiomyocytes [22]. In a recent study, Avanzato et al. investigated the role of H2S in regulating VDCCs and the related functional effects on the cardiomyoblast cell line H9c2. They found that H2S inhibits LTCCs and TTCCs in H9c2. Pretreatment with NaHS (a donor of H2S) prevented cell death via H2O2 through inhibiting LTCCs. Their results were the first to demonstrate that H2S protects rat cardiomyoblasts against oxidative stress through inhibition of LTCCs [23]. In addition, Tang et al. suggested that exogenous and endogenous H2S inhibited pancreatic insulin secretion by inhibiting LTCCs activity. They confirmed that NaHS reversibly decreased LTCC current density in a concentration-dependent manner in CSE WT pancreatic beta cells. Furthermore, they observed that DL-propargylglycine (an inhibitor of CSE) increased the basal LTCC activity in beta cells from CSE WT mice, but not in pancreatic beta cells from CSE-KO mice. Pancreatic beta cells from CSE-KO mice displayed a higher LTCCs density than those from WT mice. These results suggested that a novel mechanism for regulating insulin secretion was related to the CSE/H2S system, which controlled LTCC activity [24]. Recently, some data showed that exogenous and endogenous H2S can modify cystein residues of different proteins through S-sulfhydration. The –SH from sulfhydryl donor is transformed to free cysteine sulfhydryl and forms covalent persulfide (–SSH) [25, 26]. In 2012, Zhang and his coworkers showed that NaHS inhibited the peak amplitude of the L-type calcium current in a concentration-dependent manner and could be partly inhibited by the oxidant sulfhydryl modifier diamide (DM). They explained that dithiothreitol (DTT), a reductant that transforms disulfide bridges into sulfhydryl groups in cysteine-containing proteins, could significantly reverse NaHS-induced inhibition of calcium current from LTCCs. Their results suggested that H2S inhibited L-type calcium currents depending on the sulfhydryl group in rat cardiomyocytes [27] (Figure 1).

Bottom Line: More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration.However, the understanding of the molecular targets and mechanisms is incomplete.Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, Heilongjiang 150086, China.

ABSTRACT
A growing amount of evidence has suggested that hydrogen sulfide (H2S), as a gasotransmitter, is involved in intensive physiological and pathological processes. More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration. These groups have demonstrated the reciprocal interaction between H2S and calcium ion channels and transporters, such as L-type calcium channels (LTCC), T-type calcium channels (TTCC), sodium/calcium exchangers (NCX), transient receptor potential (TRP) channels, β-adrenergic receptors, and N-methyl-D-aspartate receptors (NMDAR) in different cells. However, the understanding of the molecular targets and mechanisms is incomplete. Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions. In this review, we elucidate that H2S controls intracellular calcium homeostasis and the underlying mechanisms.

No MeSH data available.


Related in: MedlinePlus