Abstract:Methionine and cysteine residues in proteins are the major targets of reactive oxygen species (ROS). The present work was designed to characterize the impact of methionine and cysteine oxidation upon [Ca(2+)](i) in hippocampal neurons. We investigated the effects of H(2)O(2) and chloramine T(Ch-T) agents known to oxidize both cysteine and methionine residues, and 5, 5'-dithio-bis (2-nitrobenzoic acid) (DTNB)--a cysteine-specific oxidant, on the intracellular calcium in hippocampal neurons. The results showed t… Show more
“…Our results are not likely due to CaM methionine oxidation since DTT selectively reduces cysteine residues (Ciorba et al, 1997; Cai and Sesti, 2009; Long et al, 2009). In addition, DTT had equivalent effects in activating CaMKII, regardless of whether exogenous CaM was added to the reaction.…”
The contribution of the NMDA receptors (NMDARs) to synaptic plasticity declines during aging, and the decline is thought to contribute to memory deficits. Here, we demonstrate that an age-related shift in intracellular redox state contributes to the decline in NMDAR responses through Ca 2ϩ /calmodulin-dependent protein kinase II (
“…Our results are not likely due to CaM methionine oxidation since DTT selectively reduces cysteine residues (Ciorba et al, 1997; Cai and Sesti, 2009; Long et al, 2009). In addition, DTT had equivalent effects in activating CaMKII, regardless of whether exogenous CaM was added to the reaction.…”
The contribution of the NMDA receptors (NMDARs) to synaptic plasticity declines during aging, and the decline is thought to contribute to memory deficits. Here, we demonstrate that an age-related shift in intracellular redox state contributes to the decline in NMDAR responses through Ca 2ϩ /calmodulin-dependent protein kinase II (
“…CLT is a potent oxidant of -SH groups and methionine (24). When applied extracellularly in the bath, CLT (1 mM) significantly inhibited the rvKir6.1=rvSUR1 K ATP currents from À18.6 AE 3.0 to À10.1 AE 1.9 pA=pF (n ¼ 5; p < 0.05).…”
Section: Interaction Of H 2 S and Sulfhydryl Groups Of K Atp Channelsmentioning
Hydrogen sulfide (H(2)S) is an endogenous opener of K(ATP) channels in many different types of cells. However, the molecular mechanism for an interaction between H(2)S and K(ATP) channel proteins remains unclear. The whole-cell patch-clamp technique and mutagenesis approach were used to examine the effects of H(2)S on different K(ATP) channel subunits, rvKir6.1 and rvSUR1, heterologously expressed in HEK-293 cells. H(2)S stimulated coexpressed rvKir6.1/rvSUR1 K(ATP) channels, but had no effect on K(ATP) currents generated by rvKir6.1 expression alone. Intracellularly applied sulfhydryl alkylating agent (N-ethylmaleimide, NEM), oxidizing agent (chloramine T, CLT), and a disulfide bond-oxidizing enzyme (protein disulfide isomerase) did not alter H(2)S effects on this recombinant channels. CLT, but not NEM, inhibited basal rvKir6.1/rvSUR1 currents, and both abolished the stimulatory effects of H(2)S on K(ATP) currents, when applied extracellularly. After selective cysteine residues (C6S and C26S but not C1051S and C1057S) in the extracellular loop of rvSUR1 subunits were point-mutated, H(2)S lost its stimulatory effects on rvKir6.1/rvSUR1 currents. Our results demonstrate that H(2)S interacts with Cys6 and Cys26 residues of the extracellular N terminal of rvSUR1 subunit of K(ATP) channel complex. Direct chemical modification of rvSUR1 subunit protein constitutes a molecular mechanism for the activation of K(ATP) channels by H(2)S.
“…Physiological level of H 2 S is in wide range between 15 nM and 300 μM depending on detection methods and the tissues analyzed [ [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] ]. In fact, the concentration of free H 2 S in vascular tissues is around 100 times greater than that in the other tissues [ 26 , 32 ], implying that H 2 S is critical in the regulation of vascular homeostasis, endothelial function and angiogenic property of ECs. Fig.…”
Diabetes is one of the most prevalent metabolic disorders and is estimated to affect 400 million of 4.4% of population worldwide in the next 20 year. In diabetes, risk to develop vascular diseases is two-to four-fold increased. Ischemic tissue injury, such as refractory wounds and critical ischemic limb (CLI) are major ischemic vascular complications in diabetic patients where oxygen supplement is insufficient due to impaired angiogenesis/neovascularization. In spite of intensive studies, the underlying mechanisms of diabetes-impaired ischemic tissue injury remain incompletely understood. Hydrogen sulfide (H
2
S) has been considered as a third gasotransmitter regulating angiogenesis under physiological and ischemic conditions. Here, the underlying mechanisms of insufficient H
2
S-impaired angiogenesis and ischemic tissue repair in diabetes are discussed. We will primarily focuses on the signaling pathways of H
2
S in controlling endothelial function/biology, angiogenesis and ischemic tissue repair in diabetic animal models. We summarized that H
2
S plays an important role in maintaining endothelial function/biology and angiogenic property in diabetes. We demonstrated that exogenous H
2
S may be a theraputic agent for endothelial dysfunction and impaired ischemic tissue repair in diabetes.
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