Search Results (132)

The canonical transsulfuration (TSS) pathway enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH) are traditionally recognized for their roles in the sequential conversion of homocysteine to cysteine and in endogenous hydrogen sulfide (H₂S) production. Increasing evidence, however, suggests that these enzymes may also exhibit non-canonical (“moonlighting”) functions that extend beyond metabolic regulation. In this review, we evaluate the hypothesis that CTH may participate in translational regulation, particularly in the control of hypoxia-inducible factor-1α (HIF-1α) expression in clear cell ovarian carcinoma (CCOC). We first highlight limitations of the prevailing H₂S- and cysteine-centric view of the TSS pathway, which may not fully explain emerging context-dependent functions of CTH in cancer biology. Current evidence suggests that CTH enhances HIF-1α protein expression through mechanisms independent of transcription, protein stability, or H₂S production, implicating a potential role in translational regulation, although direct mechanistic evidence remains limited. To critically evaluate this emerging hypothesis, we categorize evidence according to its level of experimental support, ranging from direct experimental evidence to indirect mechanistic observations and computational predictions. Within this framework, we examine three non-mutually exclusive models: (1) regulation through PI3K/AKT/mTOR-dependent translational signaling; (2) modulation of translational control through interaction with translation-associated proteins and RNA-binding proteins (RBPs) involved in HIF1A mRNA regulation; and (3) the more speculative possibility of direct interaction between CTH and HIF1A mRNA. Collectively, these observations support a model in which CTH contributes to selective translational regulation beyond its canonical metabolic functions, potentially linking sulfur metabolism to stress-adaptive gene expression in cancer. Full article

Chronic kidney disease (CKD) affects approximately 700 million people worldwide and is a major contributor to end-stage renal disease (ESRD), cardiovascular morbidity, and premature mortality. Although oxidative stress has long been considered central to CKD progression, conventional antioxidant strategies have not consistently improved clinical outcomes, suggesting that excess reactive oxygen species (ROS) alone cannot fully account for the underlying disease pathophysiology. Emerging evidence supports a broader paradigm of redox network failure, characterized by the disruption of coordinated signaling among ROS, nitric oxide (NO), and reactive sulfur species (RSS). Within this framework, hydrogen sulfide (H₂S), a major endogenous RSS, functions as a key regulator of renal redox homeostasis. CKD is consistently associated with systemic and renal H₂S deficiency, accompanied by downregulation of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as impaired transsulfuration and disrupted mitochondrial sulfide oxidation. Importantly, this deficiency cannot be explained solely by reduced renal function but instead reflects active suppression of H₂S biosynthesis. Uremic toxins, particularly indoxyl sulfate (IS), contribute to this process through activation of the aryl hydrocarbon receptor (AhR), which inhibits specificity protein 1 (Sp1)-dependent transcription of H₂S-producing enzymes. This IS–AhR–Sp1 axis provides a mechanistic link between toxin accumulation and disruption of the sulfur arm of the redox network, amplifying oxidative stress, endothelial dysfunction, mitochondrial impairment, ferroptotic vulnerability, and fibrotic remodeling. Beyond H₂S itself, downstream RSS, including persulfides, polysulfides, and thiosulfate, may represent the principal bioactive mediators of sulfur-dependent redox signaling, and their coordinated depletion in CKD may impair redox buffering capacity beyond what H₂S measurement alone reflects. This review integrates current evidence to propose a conceptual model in which CKD progression involves failure of coordinated redox signaling—characterized by feed-forward network collapse and threshold-dependent transition to a self-sustaining high-ROS state—with H₂S deficiency representing one mechanistically supported component of this broader network disruption. This framework highlights the therapeutic potential of targeting redox network restoration rather than isolated oxidative pathways in CKD. Full article

“Supersulfides” is a general term for compounds containing multiple sulfur atoms within their molecules. Owing to their potent anti-oxidant and anti-inflammatory activities, these species are promising ingredients in the field of cosmetics. In this study, we elucidated the effect of silver tip (Camellia sinensis) tea on supersulfide production in epidermal keratinocytes. Silver tip extract increased the fluorescence intensity of sulfane sulfur probe 4 (SSP4) in a concentration-dependent manner and promoted supersulfide production in keratinocytes. In particular, (−)-epicatechin gallate and (−)-epigallocatechin gallate exhibited high SSP4 fluorescence intensity, indicating that these are the active components. Mechanistic analysis using quantitative polymerase chain reaction revealed that silver tip extract promotes intracellular supersulfide production by regulating supersulfide-related metabolic factors (cysteinyl-tRNA synthetase 2, cystathionine β-synthase, cystathionine γ-lyase, solute carrier family 7 member 11, and nuclear factor E2-related factor 2). Furthermore, these compounds significantly increased the supersulfide levels by reacting with sodium sulfide, a hydrogen sulfide donor, in buffer solution, thereby catalytically enhancing supersulfide production. Overall, the results of this study indicate that silver tip extract, rich in polyphenols, regulates supersulfide metabolism in keratinocytes, suggesting its potential as an anti-aging ingredient for the skin. Full article

Ischemic stroke (IS) remains a major cause of global disability and mortality. While exogenous H₂S has demonstrated neuroprotective potential, the role of endogenous H₂S generated by cystathionine β-synthase (CBS) in cerebral ischemia–reperfusion injury (CIRI) remains incompletely elucidated. L-Cysteine (L-Cys), as a substrate for CBS, serves as a key precursor for endogenous H₂S. Using the established pre-clinical model of CIRI—middle cerebral artery occlusion/reperfusion (MCAO/R) in rats—we investigated the neuroprotective effects of brain-derived CBS-generated H₂S through neurological function scoring, 2,3,5-triphenylchlorotetrazole (TTC) staining, enzyme-linked immunosorbent assay (ELISA), and histopathological examination. Immunofluorescence, Western blot, and laser speckle contrast imaging were utilized to analyze the protein expression of ZO-1, claudin-5, CBS, vascular endothelial growth factor receptor-2 (VEGFR₂) and CD31, as well as cerebral blood flux changes. L-Cys treatment ameliorated neurological deficits, reduced cerebral infarct volume, decreased serum lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) levels, attenuated histopathological damage, alleviated cerebral edema, and restored blood–brain barrier integrity via upregulation of tight junction proteins ZO-1 and claudin-5. Additionally, L-Cys improved MCAO/R-induced cognitive impairment and behavioral deficits. Furthermore, L-Cys upregulated CBS and VEGFR₂ expression, enhanced endogenous H₂S production, promoted post-ischemic cerebral angiogenesis, and improved cerebral blood flux recovery. CBS-derived H₂S promoted post-ischemic angiogenesis mediated by VEGFR₂, enhances cerebral reperfusion flux, and consequently ameliorated MCAO/R-induced CIRI in rats, providing experimental evidence for clinical translation. Full article

Cystathionine β-synthase (CBS) deficiency causes classical homocystinuria with severe hyperhomocysteinemia (HHcy) that is inadequately controlled by current therapies. We tested whether liver-targeted CBS gene therapy provides durable biochemical and phenotypic rescue. Using a Cre-inducible adult mouse model of whole-body CBS loss, a single intravenous dose of AAV-DJ-hCBS (3 × 10¹² or 3 × 10¹³ vg/kg) was administered, and the animals were followed for 12 months. Vector biodistribution showed ~100-fold hepatic enrichment over the kidney and spleen. Both doses rapidly normalized plasma homocysteine (<8 µM), maintaining correction throughout the study while preventing alopecia, weight loss, and loss of adiposity. Liver histology showed resolution of inflammation, and only 2 of 19 mice developed anti-hCBS antibodies. Liver proteomics (3998 proteins quantified) revealed CBS deficiency-associated suppression of tRNA aminoacylation and dysregulation of lipid and carbon metabolism with an HNF4A transcriptional signature, all normalized by therapy. Liver metabolomics demonstrated accumulation of S-adenosylmethionine and S-adenosylhomocysteine and disruption of phosphatidylcholine synthesis, also corrected by treatment. Plasma metabolomics revealed systemic disturbances fully normalized by hepatic CBS restoration. These findings identify the liver as the central metabolic control point in CBS deficiency and support liver-targeted gene therapy as a durable corrective strategy. Full article

To explore the mechanism of action of CBS-derived H₂S in inducing cerebral vasodilation and activating BK_Ca channels. Sprague–Dawley (SD) rat middle cerebral arteries (MCA) were isolated from rat brains, and a pressure myography system was used to measure the effects of different concentrations of L-cysteine (L-Cys, 1 × 10^−5.5 to 1 × 10^−3.5 mol/L), a substrate for cystathionine-β-synthase (CBS)—a hydrogen sulfide (H₂S)-producing enzyme. Additionally, the effects of pretreatment with the CBS inhibitor amino-oxoacetate (AOAA, 1 mmol/L), the vascular endothelial growth factor receptor 2 inhibitor semaxanib (SU5416, 10 μmol/L), and the large-conductance calcium-activated potassium (BK_Ca) channel blocker iberiotoxin (IBTX, 100 nmol/L) were investigated to determine their impacts on CBS-derived H₂S-induced vasodilation. Acute digestion of rat vascular smooth muscle cells (VSMCs) was performed, and whole-cell patch-clamp techniques were used to measure current changes in neurons or astrocytes (ASTs), as well as acutely digested VSMCs, in the presence of L-Cys, AOAA (1 mmol/L), SU5416 (10 μmol/L), and IBTX (100 nmol/L). Additionally, neurons or ASTs were co-cultured with VSMCs to determine CBS-derived H₂S levels. Neurons or ASTs co-incubated with blood vessels and then treated with L-Cys produced H₂S, which exhibited a concentration-dependent dilatory effect on middle cerebral artery occlusion (MCA) pre-contracted with 100 nmol/L U46619 (p < 0.01). However, the addition of AOAA significantly attenuated this dilatory effect (p < 0.01). SU5416 and IBTX significantly inhibited cerebral vascular dilation (p < 0.01). H₂S produced by adding L-Cys after co-incubation of neurons or ASTs with VSMCs significantly increased BK_Ca channel current (p < 0.01). However, this effect was significantly attenuated after adding AOAA (p < 0.01). SU5416 and IBTX significantly inhibited the activation of BK_Ca channels (p < 0.01). Wild-type rat neurons or astrocytes (ASTs) were co-cultured with CSE(Cystathionine γ-lyase)-knockout vascular smooth muscle cells (VSMCs-CSE KO); the addition of L-Cys significantly increased hydrogen sulfide (H₂S) levels in the co-culture system (p < 0.01), while the addition of AOAA reduced H₂S production (p < 0.01). However, the addition of SU5416 had no statistical significance. Neurogenic H₂S, the H₂S produced by neurons and ASTs, could induce cerebral vasodilation in rats via VEGFR₂(Vascular Endothelial Growth Factor Receptor 2)-mediated activation of BK_Ca channels in the smooth muscle cells. Full article

Hydrogen sulfide (H₂S) is essential for renal function; however, it is toxic at high concentrations. H₂S is increased during reductive stress (RS). Increased antioxidant capacity and reduced/oxidized glutathione (GSH/GSSG) characterize a rat model of RS associated with chronic consumption of 6% Hibiscus sabdariffa Linnaeus (HSL). Here, we evaluate if chronic consumption of an infusion of HSL causes kidney damage associated with an increase in H₂S. Twenty-one Wistar rats were divided into three groups. Group 1: rats received plain tap water ad libitum (G1); Group 2: rats received an ad libitum infusion of 6% HSL for one month (G2); and Group 3: rats consumed a 6% HSL infusion for one month and were then given natural water for another month (G3). We evaluated renal vasodilatation, cystathionine–β–synthase (CBS), cystathionine–γ–lyase (CSE), 3–mercaptopyruvate-sulfur-transferase (3–MST), γ-glutamylcysteine synthetase (GCLC), Nrf2, total OXPHOS, H₂S concentration, GSH/GSSG and oxidized/reduced thiols in the kidney. Renal vasodilatation and total OXPHOS in complex IV and I and oxidized/reduced thiols were decreased (p ≤ 0.01) but H₂S, CBS, SCE, GCLC, and NrF2 expression and GSH/GSSG were increased (p ≤ 0.04). The HSL infusion provided cysteine that was metabolized by CBS and CSE, elevating chronic H₂S and favoring renal damage. Full article

Cerebral ischemia–reperfusion injury triggers mitochondrial dysfunction and oxidative stress, exacerbating neuronal apoptosis. Emerging evidence highlights hydrogen sulfide (H₂S) as a gasotransmitter modulating redox balance, autophagy, and apoptosis. This study investigates the neuroprotective mechanisms of Enriched Environment (EE) against ischemic injury, focusing on mitochondrial dynamics and H₂S-mediated pathways. Using MCAO mice and OGD/R-treated SH-SY5Y neurons, interventions targeting H₂S synthesis, hypoxia-inducible factor 1-alpha (HIF-1α), and mitophagy were implemented. Behavioral, histological, and molecular analyses demonstrated EE significantly improved neurological outcomes, suppressed apoptosis, and attenuated oxidative damage (reduced MDA, elevated MnSOD/glutathione). Mechanistically, EE enhanced mitophagy via dual pathways: canonical PINK1/parkin-mediated mitochondrial clearance, corroborated by transmission electron microscope and LC3B/parkin colocalization, and non-canonical HIF-1α/BNIP3L axis activation. Transcriptomic and Co-immunoprecipitation (Co-IP) data revealed EE upregulated endogenous H₂S biosynthesis post-injury by promoting dopamine-induced calcium influx, which activated calmodulin-dependent signaling to stimulate cystathionine β-synthase/γ-lyase expression. Pharmacological blockade of H₂S synthesis or HIF-1α abolished mitochondrial protection, confirming H₂S as a central mediator. Notably, H₂S exerted antiapoptotic effects by restoring mitochondrial integrity through synergistic mitophagy activation and oxidative stress mitigation. These findings propose a novel neuroprotective cascade: EE-induced dopaminergic signaling potentiates H₂S production, which coordinates PINK1/parkin and HIF-1α/BNIP3L pathways to eliminate dysfunctional mitochondria, thereby preserving neuronal homeostasis. This study elucidates therapeutic potential of EE via H₂S-driven mitochondrial quality control, offering insights for ischemic brain injury intervention. Full article

Recent scientific reports have highlighted the physiological role, toxicological effects, and pathophysiological aspects of gasotransmitters, particularly hydrogen sulfide (H₂S), which is recognized as a new member of this family. Endogenous generation of H₂S in the skin occurs through both enzymatic and non-enzymatic pathways. The main enzymes involved in its endogenous production are cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST) and cysteine aminotransferase. 3-MST and CSE are crucial for maintaining the epidermal barrier. H₂S may play a role in oncogenesis, acting as a gas signaling molecule that disrupts mitochondrial respiration and influences immune modulation, cell proliferation, apoptosis, tumor cell survival, and metastasis. Interestingly, H₂S exhibits dual effects in the biology of skin cancer, promoting tumor growth in some contexts and exerting antitumor activities in others. Data from the European Cancer Information System and Global Cancer Observatory show a significant global increase in skin cancer cases. The most common types of cutaneous malignancies, from both epidemiological and clinical perspectives, are basal cell carcinoma. squamous cell carcinoma, and melanoma. This review aims to evaluate the dysfunctional metabolism of H₂S and the specific profiles of the enzymes that synthesize H₂S in skin cancer. By comparing the roles of H₂S in normal cells with those in cancer cells, we can enhance current understanding of its implications in skin cancer biology. This research paves the way for new clinical strategies, including the development of H₂S-modulatory therapies tailored to the dynamics of tumor progression, which could help overcome therapeutic resistance. Full article

Gliomas are central nervous system primary tumors that are distinguished by heterogeneity, broad-based infiltration, and metabolic reprogramming that sustains proliferation, invasion, and therapy refractoriness. Oxidative stress—a state of imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense—and disturbed iron metabolism are central drivers of glioma biology. The aim of this study was to evaluate ROS production, sulfane sulfur levels, the expression of proteins with antioxidant properties, such as L-cysteine-metabolizing enzymes (cystathionine β-synthase, CBS; cysteine dioxygenase 1, CDO1; cystathionine γ-lyase, CTH; 3-mercaptopyruvate sulfurtransferase, MPST; thiosulfate sulfurtransferase, TST) and non-enzymatic proteins (p53; transferrin receptor 1, TfR1), in human brain cancer cells differing in malignancy: 1321N1 astrocytoma and T98G glioblastoma. Western blotting analysis demonstrated that the expression of CBS, CDO1, and TfR1 was significantly increased in T98G cells, while CTH, MPST, TST, and p53 were comparably expressed in both cell lines. Quantitative assays revealed that T98G cells harbored significantly higher sulfane sulfur levels and higher numbers of ROS-positive cells compared to 1321N1 cells. Our results suggest that glioblastoma but not astrocytoma cells adapt sulfur and iron metabolism to provide proliferation capacity against chronic oxidative stress. It seems that CBS as well as CDO1 may significantly increase the antioxidant potential of T98G cells. In summary, this study suggests a differing metabolic vulnerability identifiable only in high-grade glioma cells and provides a potential novel molecular target for therapy. Full article

Background: Neonatal seizures are critical neurological events with long-term implications for brain development. Standard antiseizure medications, such as phenobarbital, often yield suboptimal seizure control and may be associated with neurotoxicity. This narrative review explores the role of vitamin B6 as a precision therapy in neonatal seizure syndromes, particularly in pyridoxine-responsive conditions. Methods: We conducted a narrative review of the biochemical functions of vitamin B6, focusing on its active form, pyridoxal 5′-phosphate (PLP), and its role as a coenzyme in neurotransmitter synthesis. We examined the genetic and metabolic disorders linked to vitamin B6 deficiency, such as mutations in pyridox(am)ine 5’-phosphate oxidase (PNPO), Aldehyde Dehydrogenase 7 Family Member A1 (ALDH7A1), alkaline locus phosphatase (ALPL), and cystathionine β-synthase (CBS), and discussed the clinical rationale for empirical administration in acute neonatal seizure settings. Results: Vitamin B6 is essential for the synthesis of gamma-aminobutyric acid (GABA), dopamine, and serotonin, with PLP-dependent enzymes such as glutamic acid decarboxylase and aromatic L-amino acid decarboxylase playing central roles. Deficiencies in PLP due to genetic mutations or metabolic disruptions can result in treatment-resistant neonatal seizures. Early supplementation, especially in suspected vitamin B6-dependent epilepsies, may provide both diagnostic clarity and seizure control, potentially reducing exposure to conventional antiseizure medications. Conclusions: Vitamin B6-responsive epilepsies highlight the clinical value of mechanism-based, individualized treatment approaches in neonatology. Incorporating genetic and metabolic screening into seizure management may improve outcomes and aligns with the principles of precision medicine. Full article

Pre-eclampsia (PE) is a hypertensive pregnancy complication. Oxidative stress is hypothesized to contribute to the pathophysiology of PE. Both the hydrogen sulfide (H₂S) and oxytocin (OT) systems might play a role in the pathophysiology of PE, like their antioxidant and hypotensive effects. Thus, the role of the interaction of the OT and H₂S systems in the context of PE was further elucidated in the present clinical case–control study “NU-HOPE” (Nürnberg-Ulm: The role of H₂S and Oxytocin Receptor in Pre-Eclampsia; ethical approval by the Landesärztekammer Bayern, file number 19033, 29 August 2019), comparing uncomplicated pregnancies, early onset PE (ePE, onset < 34 weeks gestational age) and late onset PE (lPE, onset > 34 weeks gestational age). Routine clinical data, serum H₂S and homocysteine levels, and tissue protein expression, as well as nitrotyrosine formation, were determined. The main findings were (i) unchanged plasma sulfide levels, (ii) significantly elevated homocysteine levels in ePE, but not lPE, (iii) significantly elevated expression of H₂S enzymes and OT receptor in the placenta in lPE, and (iv) significantly elevated nitrotyrosine formation in the lPE myometrium. Taken together, these findings suggest a role for the interaction of the endogenous H₂S- and OT/OTR systems in the pathophysiology of pre-eclampsia, possibly linked to impaired antioxidant protection. Full article

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H₂S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of H₂S production in flies showed minimal levels in the double- and triple-knockout strains. The double- (cbs-/-; cse-/-) and triple- (cbs-/-; cse-/-; dtst-/-) KO flies exhibited a shortened lifespan and reduced fecundity, and showed dramatic changes in Malpighian tubule morphology. The transcriptomic analysis revealed a profound increase in the expression levels of several genes involved in excretory system function in the double-KO and especially the triple-KO flies. Importantly, major groups of differentially expressed genes (DEGs) in the whole bodies of females and ovaries of KO strains included genes responsible for detoxification, reproduction, mitochondrial activity, excretion, cell migration, and muscle system function. The reduced fecundity observed in the double- and triple-KO flies correlated with pronounced changes in the ovarian transcriptome. At the same time, the single knockout of dtst1 increased the flies’ fecundity and lifespan. Our experiments exploring unique Drosophila strains with KO of major H₂S-related genes revealed several new pathways controlled by this ancient adaptogenic system that is involved in various human diseases and aging. Full article

Background: Homocystinuria caused by cystathionine β-synthase (CBS) deficiency is the most common congenital disorder related to sulfur amino acid metabolism, manifested by neurological, vascular, and connective tissue involvement. Methods: This study analyzed the pathogenic gene and molecular mechanism of two classic homocystinuria families through whole exome sequencing and in vitro experiments including minigene assay and expression analysis. Results: Both probands presented with ectopia lentis, high myopia, and abnormally elevated homocysteine level, but one of them had more severe clinical manifestations, including general growth retardation, mild intellectual disability, and severe pectus excavatum. Their family members were phenotypically normal but presented slightly higher levels of homocysteine in plasma. Whole exome sequencing revealed that the two probands carried c.833T>C (p.Ile278Thr) and c.1359-1G>C, and c.919G>A (p.Gly307Ser) and c.131delT (p.Tle44Thrfs*38) compound heterozygous mutations in the CBS gene, respectively. Bioinformatics and in vitro functional analysis showed that the c.1359-1G>C mutation affects the normal splicing of CBS gene, resulting in the production of two abnormal transcripts and the production of two truncated proteins. One of the c.1359-1G>C splicing events (c.1359_1467del) and c.131delT (p.Tle44Thrfs*38) both lead to a significant decrease in CBS mRNA and protein levels. Conclusions: Accurate diagnosis of patients with homocystinuria is of great importance for timely and effective treatment, as well as for the provision of appropriate genetic counseling and prenatal diagnosis guidance to the affected families. Full article

Background/Objectives: Hydrogen sulfide (H₂S) is a vasorelaxant gas and exerts anti-oxidative, anti-inflammatory, and cytoprotective effects. H₂S has been implicated in regulating placental vaso-activity and angiogenesis. It is believed that abnormal trophoblast production of vasodilators and angiogenic factors contributes to pre-eclampsia development. However, little is known about whether aberrant H₂S production is present in placental trophoblasts from pre-eclamptic pregnancies. Methods: Trophoblasts were isolated from normal and pre-eclamptic placentas. After incubation, cell production of H₂S in the culture medium and the cellular levels of H₂S were analyzed by reversed phase high-performance liquid chromatography (RP-HPLC). Expression levels of the three key H₂S converting enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), were determined by immunohistochemistry. The protein expression of CBS and CSE was assessed by Western blot analysis. Results: (1) Trophoblast production and cellular levels of H₂S were significantly reduced in cells from pre-eclamptic vs. normal placentas; (2) free H₂S production was increased in a time-dependent manner in cultured trophoblasts from normal, but not from pre-eclamptic, placentas; and (3) strong CBS and CSE expression was seen in trophoblasts from normal, as opposed to pre-eclamptic, placentas. Reduced CBS and CSE expression in trophoblasts from pre-eclamptic vs. normal placentas were confirmed by Western blot analysis; and (4) 3-MST expression was undetachable in both normal and pre-eclamptic placentas, but 3-MST expression was strongly expressed in the first and second trimester placentas. Conclusions: These data provide plausible evidence that downregulation of CBS and CSE, but not 3-MST, expression may be responsible for reduced free H₂S production and decreased cellular H₂S levels in pre-eclamptic placentas. Our data provide further evidence that expression of 3-MST in placental trophoblasts is likely gestational age (developmental)-dependent. Full article