Superoxide stimulates IP3-induced Ca2+ release from vascular smooth muscle sarcoplasmic reticulum

Abstract

Reactive oxygen intermediates (ROI) have been implicated in a variety of pathophysiological conditions, and vascular smooth muscle may be a site of damage in such oxygen toxicity. Mechanisms of the effects of these intermediates on vascular smooth muscle at the cellular level, however, have not been well studied. We have previously shown that xanthine oxidase (XO)-generated superoxide radicals (O2-.) inhibited the Ca(2+)-adenosine triphosphatase of vascular smooth muscle sarcoplasmic reticulum (SR) through mechanisms that do not involve H2O2 or hydroxyl radicals. In the present study, we report that the D-myo-inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release from bovine aortic SR was also affected by O2-(.). Hypoxanthine (100 microM) plus XO (10 mU/ml) in the presence of catalase (100 U/ml) stimulated the IP3-induced Ca2+ release from SR monitored using arsenazo III. At 10 microM IP3, the release was doubled by O2-. treatment. As a consequence of using the higher SR protein concentrations required to observe the Ca2+ release, this effect was independent of Ca2+ uptake inhibition induced by O2-(.). Since the effect of O2-. was not seen when a nonhydrolyzable analogue of IP3 was used to induce Ca2+ release, O-2. may be inhibiting the degradation processes of IP3.

Cross-talk between calcium and reactive oxygen species signaling

“…In neurons, activation of RyR 3 by ROS might modify Ca 2+ -dependent long-term potentiation and long-term depression [37] . In the case of IP 3 R, it has been reported that O 2 · -enhances IP 3 -induced Ca 2+ release from fractionated vascular smooth muscle SR [43] , and oxidized GSH induces Ca 2+ release from IP 3 R in intact hepatocytes [44] . Moreover, the data reported by Hu et al [45] transport by SERCA in smooth muscle cells [2] and depress cardiac sarcolemmal Ca 2+ -ATPase [46] .…”

Class A Scavenger Receptor Up-regulation in Smooth Muscle Cells by Oxidized Low Density Lipoprotein

“…Because oxidants stimulate calcium signaling (17,18), we examined the effect of the calcium ionophore A23,187 on the ability of H/V or cell-modified LDL to regulate receptor activity (Fig. 7A).…”

“…Oxidants stimulate Ca 2ϩ signaling by increasing cytosolic Ca 2ϩ concentration (17,18). The cellular oxidative stress generated by oxidized LDL has been associated with a rise in free cytosolic calcium (50).…”

“…Reactive oxygen species (ROS), such as superoxide anions and H 2 O 2 , function as second messengers in signal transduction, mediating ligand stimulation by tyrosine phosphorylation (16). Ca 2ϩ signaling is also thought to contribute to ROS-induced gene expression (17,18). Downstream targets of ROS include the stress-activated c-Jun amino-terminal kinase (JNK) (19), which phosphorylates and activates c-Jun.…”

The Cross-Talk Between Mitochondria and the Nucleus in the Response to Oxidative Stress Associated with Mitochondrial Dysfunction in Mitochondrial Encephalomyopathies

“…More and more studies have supported that ROS and cellular redox state can directly modulate Ca 2+ signaling through regulation of ion transporters (Hool & Corry, 2007). ROS have been shown to increase the Ca 2+ channel activity through directly oxidizing the redox-sensing thiols on the Ryanodine receptor channel, and thereby induce the Ca 2+ uptake from plasma membrane (Werth & Thayer, 1994), and on IP3 receptor mediating Ca 2+ release from ER which leads to elevated cytosolic Ca 2+ (Suzuki & Ford, 1992). On the other hand, alteration of cellular redox states such as the lower GSH/GSSG and NADH/NAD + ratios have been reported to modulate Ca 2+ homeostasis by elevating the activity of Ca 2+ channels and inhibiting the Ca 2+ pump (Kourie, 1998;Zima et al, 2004).…”