Examining the fundamental biology of a novel population of directly reprogrammed human neural precursor cells.

Background: Cell reprogramming is a promising avenue for cell-based therapies as it allows for the generation of multipotent, unipotent, or mature somatic cells without going through a pluripotent state. While the use of autologous cells is considered ideal, key challenges for their clinical translation include the ability to reproducibly generate sufficient quantities of cells within a therapeutically relevant time window.

Methods: We performed transfection of three distinct human somatic starting populations of cells with a non-integrating synthetic plasmid expressing Musashi 1 (MSI1), Neurogenin 2 (NGN2), and Methyl-CpG-Binding Domain 2 (MBD2).

The interaction of estrogen and CSE/HS pathway in the development of atherosclerosis.

Both estrogen and hydrogen sulfide (HS) have been shown to inhibit the development of atherosclerosis. We previously reported that cystathionine γ-lyase knockout (CSE-KO) male mice develop atherosclerosis earlier than male wild-type (WT) mice. The present study investigated the interaction of CSE/HS pathway and estrogen on the development of atherosclerosis in female mice.

Hydrogen sulfide and the liver.

Hydrogen sulfide (H2S) is a gasotransmitter that regulates numerous physiological and pathophysiological processes in our body. Enzymatic production of H2S is catalyzed by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST). All these three enzymes present in the liver and via H2S production regulate liver functions.

Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis.

Background: Cystathionine γ-lyase (CSE) produces hydrogen sulfide (H2S) in the cardiovascular system. The deficiency of CSE in mice leads to a decreased endogenous H2S level, an age-dependent increase in blood pressure, and impaired endothelium-dependent vasorelaxation. To date, there is no direct evidence for a causative role of altered metabolism of endogenous H2S in atherosclerosis development.

Hydrogen sulfide and the pathogenesis of atherosclerosis.

Significance: Stigmatized as a toxic environmental pollutant for centuries, hydrogen sulfide (H2S) has gained recognition over the last decade as an important gasotransmitter that functions in physiological and pathophysiological conditions, such as atherosclerosis.

Recent Advances: Atherosclerosis is a common disease that stems from the buildup of fatty/cholesterol plaques on the endothelial cells of arteries. The deposits mitigate thickening and stiffening of arterial tissue, which contributes to concomitant systemic or localized vascular disorders.

Hydrogen sulfide protects against cellular senescence via S-sulfhydration of Keap1 and activation of Nrf2.

Aims: H2S, a third member of gasotransmitter family along with nitric oxide and carbon monoxide, exerts a wide range of cellular and molecular actions in our body. Cystathionine gamma-lyase (CSE) is a major H2S-generating enzyme in our body. Aging at the cellular level, known as cellular senescence, can result from increases in oxidative stress.

Interaction of hydrogen sulfide and estrogen on the proliferation of vascular smooth muscle cells.

Hydrogen sulfide (H(2)S) can be endogenously generated from cystathionine gamma-lyase (CSE) in cardiovascular system, offering a cardiovascular protection. It is also known that the lower risk of cardiovascular diseases in female is partially attributed to the protective effect of estrogen. The current study explores the interaction of H(2)S and estrogen on smooth muscle cell (SMC) growth.

Integrated stress response modulates cellular redox state via induction of cystathionine γ-lyase: cross-talk between integrated stress response and thiol metabolism.

The integrated stress response mediated by eukaryotic translation initiation factor 2α (eIF2α) phosphorylation maintains cellular homeostasis under endoplasmic reticulum (ER) stress. eIF2α phosphorylation induces activating transcription factor 4 (ATF4), a basic leucine zipper transcription factor that regulates the expression of genes responsible for amino acid metabolism, cellular redox state, and anti-stress responses. Cystathionine γ-lyase (CSE) and cystathionine β-synthase are critical enzymes in the transsulfuration pathway, which also regulate cellular redox status by modulating glutathione (GSH) levels.

A critical life-supporting role for cystathionine γ-lyase in the absence of dietary cysteine supply.

This study examined the important relationship between cystathionine γ-lyase (CSE) functionality and cysteine supply for normal growth and life span. Mice with a targeted deletion of the CSE gene (CSE-KO) were fed a cysteine-limited diet and their growth and survival patterns as well as levels of cysteine, homocysteine, glutathione, and hydrogen sulfide (H2S) were measured. CSE-KO mice fed a cysteine-limited diet exhibited growth retardation; decreased levels of cysteine, glutathione, and H2S; and increased plasma homocysteine level.

Cystathionine gamma-lyase deficiency and overproliferation of smooth muscle cells.

Aims: Cystathionine gamma-lyase (CSE)-derived H2S plays an important role in regulating cell growth. Lack of CSE expression results in development of hypertension. The current study compared proliferation of smooth muscle cells derived from CSE gene knockout mice (SMCs-KO) with that of wild-type mice (SMCs-WT).