Overproduction of hydrogen sulfide, generated by cystathionine β-synthase, disrupts brain wave patterns and contributes to neurobehavioral dysfunction in a rat model of down syndrome

Emerging roles of cystathionine β-synthase in various forms of cancer

“…Subsequent studies demonstrated the appearance of this truncated form in cells and animals exposed to pro-inflammatory conditions [ 36 ] or to hypoxia [ 37 ]. The 45 kDa CBS is also present in various cancer cells [ 38 ] and in several brain regions of rats in a Down syndrome model that contains a triplicated (extra) copy of CBS [ 39 ]. The truncated form of CBS no longer contains its allosteric regulatory domain and is in a constitutively active (“hyperactive”) form capable of higher rate of H 2 S generation than the normal isoform [ 33 , 34 ].…”

Role of the cystathionine β-synthase / H2S pathway in the development of cellular metabolic dysfunction and pseudohypoxia in down syndrome

“…In other cell types – e.g. DS cells – excess H 2 S can inhibit mitochondrial Complex IV activity [ 8 ] (see also above) without affecting the expression level of Complex IV (or of other electron transport proteins) [ 8 ].…”

“…As a result of the “gene dosage effect”, CBS is overexpressed in DS, and this has been long suspected to be a ‘master switch’ in the pathophysiology of DS [ 5 , 6 ]. However, its functional role in cellular and animal models of DS has only been directly confirmed in recent studies [ 7 , 8 ]. Our group has demonstrated that human DS fibroblasts exhibit a significant bioenergetic and mitochondrial defect, which is, to a large part due to the inhibitory effect of CBS-derived H 2 S on the activity of mitochondrial Complex IV [ 9 ].…”

“…Our group has demonstrated that human DS fibroblasts exhibit a significant bioenergetic and mitochondrial defect, which is, to a large part due to the inhibitory effect of CBS-derived H 2 S on the activity of mitochondrial Complex IV [ 9 ]. Moreover, in rodent DS models that involve the triplication of CBS, the presence of CBS, and the generation of H 2 S has been causally linked to neurocognitive dysfunction [ [7] , [8] ]. However, there are no studies which systematically investigate the cellular biochemical and bioenergetic alterations caused by CBS in DS.…”

Hydrogen Sulfide Biology and Its Role in Cancer

“…Researchers have found that H 2 S-synthesizing enzymes are increased in various human malignancies, including colon cancer, prostate cancer, breast cancer, urothelial, ovarian, oral squamous cells, and thyroid cancers, and a worse prognosis mediates the tumor to advance stages [ 124 , 153 , 154 ]. To reveal these associations between H 2 S levels and cancer progression, many novel types of research have recently been published in reputed journals [ 155 , 156 , 157 , 158 , 159 , 160 ]. Recently, two novel studies from China, published in a cancer letter, unknotted this highly recommended and awaited work, and evaluated the potential impact of H 2 S inhibition and H 2 S donation, respectively, on cancer cells [ 5 , 56 ].…”