Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling

Sun, Yan; Tian, Yuan; Mainali, Prabha; Liu, Die; Chen, Stella; Zhang, Rongyuan; Liu, Xueqin; Tang, Chaoshu; Tang, Xiuying; Jin, Hang; Du, Junbao

doi:10.1038/labinvest.2009.102

Cited by 83 publications

(64 citation statements)

References 28 publications

(16 reference statements)

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“…[49][50][51] Furthermore, HDX could inhibit AAT activities and the generation of endogenous SO 2 in both pulmonary tissues and myocardium. 17,18,36 The present results showed that compared with vehicle-treated cells, OA induced a marked reduction of SO 2 generation but a significant increase in O 2 À and OH À generation, which could be reversed by supplementation of SO 2 . HDX-treated cells generated significantly increased oxygen radicals and markedly upregulated caspase-3 cleavage and PARP expression, resulting in cell injury and apoptosis demonstrated by TUNEL and Hoechst staining.…”

Section: Discussionsupporting

confidence: 53%

“…16 Although the biological effects of endogenous SO 2 have yet to be discovered, SO 2 may be endogenously produced by pulmonary vessels to regulate vascular activities and may be involved in the inflammatory response in pulmonary vascular structural remodeling. 17 In addition, endogenous SO 2 could impact myocardial antioxidant capacity in rats. 18 On the basis of these discoveries, we designed in vivo and in vitro experiments to investigate whether the endogenous SO 2 /AAT1/AAT2 pathway is involved in the development of oleic acid (OA)-induced ALI in rats and its possible mechanisms.…”

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confidence: 99%

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Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Chen

Zheng

Liu

et al. 2015

Laboratory Investigation

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The role of endogenous sulfur dioxide (SO 2 ), an efficient gasotransmitter maintaining homeostasis, in the development of acute lung injury (ALI) remains unidentified. We aimed to investigate the role of endogenous SO 2 in the pathogenesis of ALI. An oleic acid (OA)-induced ALI rat model was established. Endogenous SO 2 levels, lung injury, oxidative stress markers and apoptosis were examined. OA-induced ALI rats showed a markedly downregulated endogenous SO 2 /aspartate aminotransferase 1 (AAT1)/AAT2 pathway and severe lung injury. Chemical colorimetry assays demonstrated upregulated reactive oxygen species generation and downregulated antioxidant capacity in OA-induced ALI rats. However, SO 2 increased endogenous SO 2 levels, protected against oxidative stress and alleviated ALI. Moreover, compared with OA-treated cells, in human alveolar epithelial cells SO 2 downregulated O 2 À and OH À generation. In contrast, L-aspartic acid-b-hydroxamate (HDX, Sigma-Aldrich Corporation), an inhibitor of endogenous SO 2 generating enzyme, promoted free radical generation, upregulated poly (ADP-ribose) polymerase expression, activated caspase-3, as well as promoted cell apoptosis. Importantly, apoptosis could be inhibited by the free radical scavengers glutathione (GSH) and N-acetyl-L-cysteine (NAC). The results suggest that SO 2 /AAT1/AAT2 pathway might protect against the development of OA-induced ALI by inhibiting oxidative stress.

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Section: Discussionsupporting

confidence: 53%

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confidence: 99%

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Chen

Zheng

Liu

et al. 2015

Laboratory Investigation

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“…The right lung samples were homogenized and immediately subjected to sample preparation according to the method established by Sun et al and Mitsuhashi et al [11,19] . Lung or blood samples (100 µL) were mixed with 70 µL of 0.212 mol/L sodium borohydride in 0.05 mol/L Tris-HCl (pH 8.5) and incubated at room temperature for 30 min.…”

Section: Measurement Of So 2 Concentrations In Lung Tissue and Bloodmentioning

confidence: 99%

“…SO 2 was also previously considered a risk factor for respiratory and cardiovascular disease [9] . Recently, studies have shown that SO 2 plays important pathophysiologic roles during many disease processes, including the attenuation of monocrotaline-induced pulmonary hypertension, the inhibition of hypoxic pulmonary vascular structural remodeling, protection against isoproterenol-induced myocardial injury, and the increase of myocardial antioxidant capacity [10][11][12] . However, the effects of SO 2 on ALI and its mechanisms are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis

Huang

Liu

et al. 2012

Acta Pharmacol Sin

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“…Recent studies have shown that endogenous SO 2 is generated in cardiovascular tissues, such as vascular endothelium, medial smooth muscles, right ventricle, and left ventricle (8). Similar to H 2 S, endogenous SO 2 has important physiological and pathophysiological roles, including hypotensive activity (4,18), vasodilation (8,9), inhibition of oxidative stress (3,28,48), inhibition of smooth muscle cell proliferation (17), and remodeling of pulmonary arterial endothelial cells (33), protection against myocardial ischemia/reperfusion (14,45,46), and isopropylarterenol-induced apoptosis (16). An increasing number of studies suggest that endogenous SO 2 is also a gaseous signaling molecule with a variety of cardiovascular functions, including vasodilation (24,44,26).…”

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confidence: 99%

The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization

Yao

Huang

Liu

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization. Am J Physiol Regul Integr Comp Physiol 310: R1073-R1080, 2016. First published March 23, 2016 doi:10.1152/ajpregu.00101.2015.-The present study was designed to explore the role of soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/PKG pathway in sulfur dioxide (SO 2)-induced vasodilation. We showed that SO2 induced a concentration-dependent relaxation of phenylephrine (PE)-precontracted rat aortic rings in association with an increase in cGMP concentration, whereas L-aspartic acid ␤-hydroxamate (HDX), an inhibitor of SO 2 synthase, contracted rings in a dose-dependent manner. Pretreatment of aortic rings with the sGC inhibitor ODQ (30 M) attenuated the vasodilatory effects of SO 2, suggesting the involvement of cGMP pathway in SO 2-induced vasodilation. Mechanistically, SO 2 upregulated the protein levels of sGC and PKG dimers, while HDX inhibited it, indicating SO 2 could promote cGMP synthesis through sGC activation. Furthermore, the dimerization of sGC and PKG and vasodilation induced by SO 2 in precontracted rings were significantly prevented by thiol reductants dithiothreitol (DTT). In addition, SO 2 reduced the activity of phosphodiesterase type 5 (PDE5), a cGMP-specific hydrolytic enzyme, implying that SO 2 elevated cGMP concentration by inhibiting its hydrolysis. Hence, SO2 exerted its vasodilatory effects at least partly by promoting disulfidedependent dimerization of sGC and PKG, resulting in an activated sGC/cGMP/PKG pathway in blood vessels. These findings revealed a new mode of action and mechanisms by which SO 2 regulated the vascular tone. sulfur dioxide; vasodilation; SGC; cGMP; PKG; dimer IN THE LAST DECADE, RESEARCH focusing on sulfur-containing amino acid metabolic pathways indicates that L-cysteine as a substrate cannot only generate hydrogen sulfide (H 2 S) through transsulfuration under cystathionine-␥-lyase or cystathionine-␥-synthase catalysis (35), but also endogenously generate sulfur dioxide (SO 2 ) under cysteine dioxygenase oxidation and aspartate aminotransferase (AAT) transamination (32). Recent studies have shown that endogenous SO 2 is generated in cardiovascular tissues, such as vascular endothelium, medial smooth muscles, right ventricle, and left ventricle (8). Similar to H 2 S, endogenous SO 2 has important physiological and pathophysiological roles, including hypotensive activity (4, 18), vasodilation (8, 9), inhibition of oxidative stress (3,28,48), inhibition of smooth muscle cell proliferation (17), and remodeling of pulmonary arterial endothelial cells (33), protection against myocardial ischemia/reperfusion (14,45,46), and isopropylarterenol-induced apoptosis (16). An increasing number of studies suggest that endogenous SO 2 is also a gaseous signaling molecule with a variety of cardiovascular functions, including vasodilation (24,44,26). Previous studies have shown that SO 2 could activate the calcium and potassium channels by i...

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Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling

Cited by 83 publications

References 28 publications

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis

The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization

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