Calcium ionophoric activity

Dahlgren, C. (1987). Difference in extracellular radical release after chemotactic factor and calcium ionophore activation of the oxygen radical-generating system in human neutrophils. Biochim. Biophys. Acta 930, 33-8. 

Historically, enzyme catalysis has played a highly prominent role, with the first enzyme-catalyzed asymmetric addition of HCN to aldehydes dating back to 1908 [167]. A wide range of both aromatic and aliphatic ketones are suitable substrates and produce cyanohydrins of high optical purity. The most readily available and hence most commonly employed enzyme for asymmetric cyanohydrin formation is (R)-hydroxynitrile lyase isolated from almonds. Recent cloning and over-expression techniques have also made a number of (S)-hydroxynitrile lyases available for organic synthesis [164, 165]. This was utilized in Griengl s synthesis of coriolic acid (255), a natural product that displays calcium ionophoric activity and acts as a prostacyclin mimic (Scheme 2.32) [168]. Thus, an (S)-hydroxynitrile lyase was cloned from rubber trees (Hevea brasiliensis), overexpressed in Pichia pastoris, and used to provide cyanohydrin 254 in 99 % ee. 

As expected, ionomycin, a calcium ionophore, causes a sustained rise in the free intracellular concentration to approximately 450 nM (Figure 4). In this system, pardaxin induced an increase in intracellular [Ca ] only in the presence of extracellular Ca (Figure 4). These results indicate that pardaxin mediated a Ca influx but did not release Ca from intracellular stores. This influx is most probably mediated directly by pardaxin channels and possibly also indirectly by activation of the Ca channels of the chromaffin cells by the depolarization produced by the pardaxin channels (data not shown). These observations further substantiate our hypothesis 10) that transmembrane fluxes of Na and Ca are involved in the pathological action of pardaxin. 

MF effects on FA relatives and healthy donors. (Fanconi anemia is an autosomal recessive disease associated with the overproduction of free radicals, Chapter 31.) It has been shown earlier [215] that FA leukocytes produce the enhanced amount of hydroxyl or hydroxyl-like free radicals, which are probably formed by the Fenton reaction. It was suggested that MF would be able to accelerate hydroxyl radical production by FA leukocytes. Indeed, we found that MF significantly enhanced luminol-amplified CL produced by non-stimulated and PMA-stimulated FA leukocytes but did not affect at all oxygen radical production by leukocytes from FA relatives and healthy donors (Table 21.3). It is interesting that MF did not also affect the calcium ionophore A23187-stimulated CL by FA leukocytes, indicating the absence of the calcium-mediated mechanism of MF activity, at least for FA leukocytes. 

A23187 <2> (<2> calcium ionophore, 216% activation of ceramide kinase in A549 lung adenocarcinoma cells [6]) [6]... 

NOS3 (eNOS) Hypertension and decreased heart rate Increased plasma renin activity Lack of response to ACh and calcium ionophore Increased sensivity to phenylephrine, serotonin, and nitroglycerine Shesely et al. (1996 ) Kojda et al. (1999)... 

ER function, as can external agents such as calcium ionophores and chemical toxicants (Rao, et al., 2001) which can cause ER stress. ER responds to stress by triggering a specific signalling pathway termed the unfolded protein response (UPR). The UPR serves to protect the cell from normal variations that occur in the cellular environment (Ma, et al., 2004, Rao, et al., 2001). Recent evidence suggests that the UPR can also be activated in tumours (Ma, et al., 2004). 

APP cleavage to occur (Shi et al., 2001), and removal is carried out by furin, a member of the pro-protein convertase enzymes (Bennett et al., 2000). Furin is a calcium dependent protease and so increases in calcium lead to an increase in activity. Treatment of cells with a calcium ionophore (A23187), which depleted intracellular stores of calcium, leads to a reduction in both furin and BACE activity (Bennett et al., 2000) and thus demonstrates one pathway through how intracellular calcium can regulate A 3 production through BACE. 

Iridoids represent a class of 941 known cyclopentano[c]pyran monoterpenoids [3] and have been reported with hepatoprotective, choleretic, vasoconstriction, anti-viral, anti-microbial, anti-inflammatory and analgesic activities. Seven iridoid glycosides, isolated from Scrophularia scorodonia L. (Scrophulariaceae), have been evaluated for effects on PGE2, and LTC4 production using calcium ionophore stimulated mouse peritoneal... 

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