Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation

Bibli, Sofia Iris; Hu, Jiong; Leisegang, Matthias; Wittig, Janina; Zukunft, Sven; Kapasakalidi, Andrea; Fißlthaler, Beate; Tsilimigras, Diamantis I.; Zografos, Georgios; Filis, Konstantinos; Brandes, Ralf P.; Papapetropoulos, Andreas; Sigala, Fragiska; Fleming, Ingrid

doi:10.1016/j.redox.2019.101379

Cited by 41 publications

(31 citation statements)

References 56 publications

(82 reference statements)

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“…Bibli et al ( 30 ) found that treatment with SG1002 of human umbilical vein endothelial cells induced protein S-sulfhydration and concomitantly protected membrane lipids from peroxidation; these in vitro findings are consistent with the significant increases in H 2 S and/or SS levels of blood and tissues attained when SG1002 is orally administered to mice ( 134 ), swine ( 210 ), and humans ( Fig. 4 ) ( 196 ).…”

Section: Sg1002: An Overviewmentioning

confidence: 58%

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SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Gojon¹,

Morales²

2020

Antioxidants & Redox Signaling

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Significance: Sulfur has a critical role in protein structure/function and redox status/signaling in all living organisms. Although hydrogen sulfide (H 2 S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H 2 S/SS in blood and/or tissues, and are amenable to treatment by H 2 S supplementation, development of safe and efficacious H 2 S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents. Recent Advances: Supramolecular tuning of the properties of well-known molecules comprising chains of sulfur atoms (diallyl trisulfide [DATS], S 8) was shown to lead to improved donors such as DATS-loaded polymeric nanoparticles and SG1002. Encouraging results in animal models have been obtained with SG1002 in heart failure, atherosclerosis, ischemic damage, and Duchenne muscular dystrophy; with TC-2153 in Alzheimer's disease, schizophrenia, age-related memory decline, fragile X syndrome, and cocaine addiction; and with DATS in brain, colon, gastric, and breast cancer. Critical Issues: Mode-of-action studies on allyl polysulfides, benzyl polysulfides, ajoene, and 12 ringsubstituted organic disulfides and thiosulfonates led several groups of researchers to conclude that the anticancer effect of these compounds is not mediated by H 2 S and is only modulated by reactive oxygen species, and that their central model of action is selective protein S-thiolation. Future Directions: SG1002 is likely to emerge as the H 2 S donor of choice for acquiring knowledge on this gasotransmitter's effects in animal models, on account of its unique ability to efficiently generate H 2 S without byproducts and in a slow and sustained mode that is dose independent and enzyme independent. Efficient tuning of H 2 S donation characteristics of DATS, dibenzyl trisulfide, and other hydrophobic H 2 S prodrugs for both oral and parenteral administration will be achieved not only by conventional structural modification of a lead molecule but also through the new ''supramolecular tuning'' paradigm. Antioxid. Redox Signal. 33, 1010-1045.

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Section: Sg1002: An Overviewmentioning

confidence: 58%

“…Participants Country: Mexico (State University of Nuevo León, UANL, Monterrey) Infertile men recruited from UANL's Reproductive Biology Clinic at the University Hospital. Mean age: 34.23 (range[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. n = 44 men completed the study.…”

mentioning

confidence: 99%

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Gojon¹,

Morales²

2020

Antioxidants & Redox Signaling

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“…Unlike apoptosis, ferroptosis is characterized by excess reactive oxygen species (ROS) and intracellular iron 5 . Superabundant ROS induces peroxidation and disintegration of lipid membrane and cell death 6 . Regulation of ferroptosis mainly depends on neutral reaction between reduced glutathione (GSH) and ROS 7 .…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between noncoding RNAs and ferroptosis: new dawn for overcoming cancer progression

Zhang

Wang

et al. 2020

Cell Death Dis

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Cancer progression including proliferation, metastasis, and chemoresistance has become a serious hindrance to cancer therapy. This phenomenon mainly derives from the innate insensitive or acquired resistance of cancer cells to apoptosis. Ferroptosis is a newly discovered mechanism of programmed cell death characterized by peroxidation of the lipid membrane induced by reactive oxygen species. Ferroptosis has been confirmed to eliminate cancer cells in an apoptosis-independent manner, however, the specific regulatory mechanism of ferroptosis is still unknown. The use of ferroptosis for overcoming cancer progression is limited. Noncoding RNAs have been found to play an important roles in cancer. They regulate gene expression to affect biological processes of cancer cells such as proliferation, cell cycle, and cell death. Thus far, the functions of ncRNAs in ferroptosis of cancer cells have been examined, and the specific mechanisms by which noncoding RNAs regulate ferroptosis have been partially discovered. However, there is no summary of ferroptosis associated noncoding RNAs and their functions in different cancer types. In this review, we discuss the roles of ferroptosis-associated noncoding RNAs in detail. Moreover, future work regarding the interaction between noncoding RNAs and ferroptosis is proposed, the possible obstacles are predicted and associated solutions are put forward. This review will deepen our understanding of the relationship between noncoding RNAs and ferroptosis, and provide new insights in targeting noncoding RNAs in ferroptosis associated therapeutic strategies.

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“…While laminar flow was initially demonstrated to enhance the expression of CSE and 3-MST in ECs [ 47 , 48 ], recent data are more complex. In particular, laminar flow (high shear stress) has been demonstrated to inhibit CSE expression via KLF2 regulated miRNA-27b [ 49 ], while turbulent flow (low shear stress) seems to upregulate CSE [ 50 , 51 ]. In rat aortic ECs, calcium-sensing receptors increase CSE expression in a phospho-calmodulin kinases II-dependent manner to inhibit platelet activation [ 52 ].…”

Section: Biochemistry Of H 2 S Productionmentioning

confidence: 99%

“…Most persulfidation reactions lead to target inhibition as phosphatase and tensin homolog (PTEN) [ 65 ], except for MEK1 activity, which in HUVEC leads to increased activity with DNA damage repair and senescence impairment [ 66 ]. Recently, Prx6 has been identified as a further target of sulfhydration on Cys47, which controls its decamerization and peroxidase activity [ 49 ], while the “S-sulphydrome” was identified among the many target proteins, and β3 integrin was identified as the key element of endothelial mechanotransduction [ 67 ].…”

Section: Molecular Signaling Activated By H 2 Smentioning

confidence: 99%

Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

2021

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The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vascularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools.

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Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation

Cited by 41 publications

References 56 publications

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Crosstalk between noncoding RNAs and ferroptosis: new dawn for overcoming cancer progression

Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

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