Hydrogen sulfide promotes calcium signals and migration in tumor-derived endothelial cells

Pupo, Emanuela; Fiorio, Alessandra; Avanzato, Daniele; Moccia, Francesco; Avelino-Cruz, José Everardo; Tanzi, Franco; Merlino, Annalisa; Mancardi, Daniele; Munaron, Luca

doi:10.1016/j.freeradbiomed.2011.08.007

Cited by 86 publications

(97 citation statements)

References 59 publications

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“…Importantly, NaHS causes a dose-dependent stimulation of B-TEC proliferation but had little effect on the control healthy cells [145]. VEGF-induced Ca 2+ entry was prevented by CSE blockade by PPG, albeit the physiological meaning of this process was not further investigated [145].…”

Section: The Roles Of H 2 S and No In Angiogenesismentioning

confidence: 99%

“…Therefore, it can be argued that K ATP channels are located upstream of MAPKs in the signaling pathway contributing to H 2 S-induced angiogenesis. [13,145]. Ca 2+ entry in rat aortic endothelium is supported by the reverse mode of the Na + /Ca 2+ exchanger (NCX) and sustained by K ATP channels-dependent membrane hyperpolarization [146].…”

Section: The Roles Of H 2 S and No In Angiogenesismentioning

confidence: 99%

“…Similarly, the genetic suppression of CSE attenuates VEGF-induced proliferation in bEnd3 micro-vascular ECs, whereas it does not impair the mitotic effect of basic fibroblast growth factor (bFGF) [113]. The influx of Ca 2+ triggered by VEGF into ECs might serve as a suitable signal to initiate CSE activation and H 2 S synthesis [11,110,145,147]. H 2 S also stimulates angiogenesis of ischemic tissues.…”

Section: The Roles Of H 2 S and No In Angiogenesismentioning

confidence: 99%

“…VEGF-induced Ca 2+ entry was prevented by CSE blockade by PPG, albeit the physiological meaning of this process was not further investigated [145]. In consideration of endothelial phenotypic changes observed in ECs isolated from tumour samples, the involvement of H 2 S in supporting tumour vascularisation should, therefore, be assessed by focussing on TECs rather on their normal counterparts [145]. …”

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confidence: 99%

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Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

Altaany¹,

Moccia²,

Munaron³

et al. 2014

CMC

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The endothelium is a cellular monolayer that lines the inner surface of blood vessels and plays a central role in the maintenance of cardiovascular homeostasis by controlling platelet aggregation, vascular tone, blood fluidity and fibrinolysis, adhesion and transmigration of inflammatory cells, and angiogenesis. Endothelial dysfunctions are associated with various cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction, and cardiovascular complications of diabetes. Numerous studies have established the antiinflammatory, anti-apoptotic, and anti-oxidant effects of hydrogen sulfide (H 2 S), the latest member to join the gasotransmitter family along with nitric oxide and carbon monoxide, on vascular endothelium. In addition, H 2 S may prime endothelial cells (ECs) toward angiogenesis and contribute to wound healing, aside to its well-known ability to relax vascular smooth muscle cells (VSMCs), thereby reducing blood pressure. Finally, H 2 S may inhibit VSMC proliferation and platelet aggregation. Consistently, a deficit in H 2 S homeostasis is involved in the pathogenesis of atherosclerosis and of hyperglycaemic endothelial injury. Therefore, the application of H 2 S-releasing drugs or using gene therapy to increase endogenous H 2 S level may help restore endothelial function and antagonize the progression of cardiovascular diseases. The present article reviews recent studies on the role of H 2 S in endothelial homeostasis, under both physiological and pathological conditions, and its putative therapeutic applications. Endothelial structure and functionThe endothelium lines the luminal surface of the entire vascular tree and the cardiac chambers, where it is termed endocardium. As a consequence, the endothelium presents a rather broad extension (300 to 1000 m 2 ) and weight (1.5 kg), achieving sizes comparable to other vital organs of the human body [1,2]. The endothelium can, therefore, be regarded as a real "organ spread across the organism" [3] and, as such, not only it is important for the regulation of local tissue functions, but also for maintaining the whole organism homeostasis [4]. Vascular endothelial cells (ECs) possess a polarized architecture: their luminal membrane is directly exposed to hematic constituents and circulating cells, while the basolateral surface is separated from surrounding tissues by a glycoprotein basement membrane -the sub-endothelial basement -which is formed by fibronectin, laminin, and collagen and is secreted by ECs themselves [2].Heterogeneity is, however, the hallmark of endothelium. ECs differ in morphology, function, and gene expression profile, so that even neighbouring cells from the same organ and blood vessel type exhibit distinct features [4]. For instance, vascular ECs may vary in size, shape, thickness and position of the nucleus. Albeit oriented along direction of blood flow, to attenuate the impact of shear stress forces on the vascular wall, microvascular ECs are rather thin (0.1 µm) and spindle-like, whilst their macrovascul...

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Section: The Roles Of H 2 S and No In Angiogenesismentioning

confidence: 99%

Section: The Roles Of H 2 S and No In Angiogenesismentioning

confidence: 99%

Section: The Roles Of H 2 S and No In Angiogenesismentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

Altaany¹,

Moccia²,

Munaron³

et al. 2014

CMC

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“…Moreover, TEC-mediated intracellular signalling is quite different from that observed in normal human microvascular EC (figure 1). Interestingly, proangiogenic Ca 2þ signals and their related pathways (mediated by AA, NO, H 2 S) are significantly altered in TEC compared with normal EC [13][14][15]. As an example, both AAand H 2 S-mediated Ca 2þ signals are involved in promigratory effects in TEC, but not in normal EC (figure 1).…”

Section: Introductionmentioning

confidence: 99%

Functional properties of ion channels and transporters in tumour vascularization

Fiorio

Munaron

2014

Phil. Trans. R. Soc. B

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Vascularization is crucial for solid tumour growth and invasion, providing metabolic support and sustaining metastatic dissemination. It is now accepted that ion channels and transporters play a significant role in driving the cancer growth at all stages. They may represent novel therapeutic, diagnostic and prognostic targets for anti-cancer therapies. On the other hand, although the expression and role of ion channels and transporters in the vascular endothelium is well recognized and subject of recent reviews, only recently has their involvement in tumour vascularization been recognized. Here, we review the current literature on ion channels and transporters directly involved in the angiogenic process. Particular interest will be focused on tumour angiogenesis in vivo as well as in the different steps that drive this process in vitro , such as endothelial cell proliferation, migration, adhesion and tubulogenesis. Moreover, we compare the ‘transportome’ system of tumour vascular network with the physiological one.

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A Multichannel Metabolic Pathway Interference Strategy for Complete Energy Depletion‐Mediated Cancer Therapy

Ding,

Wei,

Fang

et al. 2024

Adv Funct Materials

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Hydrogen sulfide (H2S) is being progressively integrated as an emerging inhibitor of the electron transport chain in energy interference‐based tumor therapy. However, metabolic reprogramming in cancer cells causes both oxidative phosphorylation (OXPHOS) and glycolysis to occur simultaneously, which contributes to the ineffective therapeutic effect of blocking a single pathway. To achieve complete suppression of energy production, an inorganic H2S donor ZnS@ZIF‐8@CaP nanoparticle (ZSZC NP) carrying Ca and Zn is constructed for achieving simultaneous interference of OXPHOS and glycolysis. The core–shell ZSZC nanoparticles can break down in the tumor microenvironment. This leads to a sustained H2S release and calcium overload to disrupt the normal functioning of mitochondria by inhibiting the expression of cytochrome c and causing damage to mitochondrial membrane potential. Meanwhile, the presence of Zn2+ hinders the typical process of glycolysis by impeding the functioning of lactate dehydrogenase and glyceraldehyde‐3‐phosphate dehydrogenase. The synchronous interference of OXPHOS and glycolysis hampers the energy supply to cancer cells. Additionally, H2S and calcium overload can expedite tumor necrosis in vivo by inducing cellular acidification and calcification. Therefore, this energy‐blocking strategy will completely deplete the energy reserves of cancer cells and provide new insights for exploring bioenergetic inhibition as a treatment approach.

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Hydrogen sulfide promotes calcium signals and migration in tumor-derived endothelial cells

Cited by 86 publications

References 59 publications

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

Functional properties of ion channels and transporters in tumour vascularization

A Multichannel Metabolic Pathway Interference Strategy for Complete Energy Depletion‐Mediated Cancer Therapy

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