C. elegans Aging Is Modulated by Hydrogen Sulfide and the sulfhydrylase/cysteine Synthase cysl-2

Qabazard, Bedoor; Ahmed, Samanza; Li, Ling; Arlt, Volker M.; Moore, Philip K.; Stürzenbaum, Stephen R.

doi:10.1371/journal.pone.0080135

Cited by 40 publications

(35 citation statements)

References 57 publications

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“…Loss of RtcB reduces lifespan under conditions of constant ER stress. As previously reported, wild-type animals had shortened life spans when grown on tunicamycin ( Fig 2B) [22]. RtcB mutants A tRNA halves accumulate in RtcB mutants (red arrowheads).…”

Section: Introductionsupporting

confidence: 83%

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response

et al. 2014

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RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo.

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Section: Introductionsupporting

confidence: 83%

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response

et al. 2014

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“…Another study found that aged healthy mice have high levels of CBS and suggested that maintenance (and increase) of CBS levels may sustain cortical function, preclude neuronal loss, and extend survival (Bruintjes et al , 2014). Other studies have corroborated their suggestions, finding that H2S prolonged survival in C. elegans (Qabazard et al , 2013; Qabazard et al , 2014). Consequently, modulation of H2S may be a viable strategy to maintain mitochondrial function and improve outcomes in aging individuals exposed to hypoxic ischemic injury.…”

Section: Pharmacologic Therapiesmentioning

confidence: 52%

Mitochondrial function in hypoxic ischemic injury and influence of aging

Ham

Raju

2017

Progress in Neurobiology

270

205

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Mitochondria are a major target in hypoxic/ischemic injury. Mitochondrial impairment increases with age leading to dysregulation of molecular pathways linked to mitochondria. The perturbation of mitochondrial homeostasis and cellular energetics worsens outcome following hypoxic-ischemic insults in elderly individuals. In response to acute injury conditions, cellular machinery relies on rapid adaptations by modulating posttranslational modifications. Therefore, post-translational regulation of molecular mediators such as hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), c-MYC, SIRT1 and AMPK play a critical role in the control of the glycolytic-mitochondrial energy axis in response to hypoxic-ischemic conditions. The deficiency of oxygen and nutrients leads to decreased energetic reliance on mitochondria, promoting glycolysis. The combination of pseudohypoxia, declining autophagy, and dysregulation of stress responses with aging adds to impaired host response to hypoxic-ischemic injury. Furthermore, intermitochondrial signal propagation and tissue wide oscillations in mitochondrial metabolism in response to oxidative stress are emerging as vital to cellular energetics. Recently reported intercellular transport of mitochondria through tunneling nanotubes also play a role in the response to and treatments for ischemic injury. In this review we attempt to provide an overview of some of the molecular mechanisms and potential therapies involved in the alteration of cellular energetics with aging and injury with a neurobiological perspective.

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“…NaHS and PDTC attenuated apoptosis in HUVECs, which is a key process in ED during the development of AS. Consistent with this, Qabazard et al (49) demonstrated that supplementation with GYY4137 markedly decreased oxidative stress-induced overexpression of CHOP, GRP78 and caspase-12 in endothelial cells. In addition, this study demonstrated that p38 mitogen-activated protein kinases (MAPK) demonstrated a key role in the regulation of AngII-induced ED (49).…”

Section: A B C Dmentioning

confidence: 62%

Hydrogen sulfide suppresses angiotensin II-stimulated endothelin-1 generation and subsequent cytotoxicity-induced endoplasmic reticulum stress in endothelial cells via NF-κB

Jiang

Zhou

et al. 2016

Molecular Medicine Reports

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The effects of hydrogen sulfide (H2S) and the nuclear factor κB (NF-κB) signaling pathway in angiotensin II (AngII)-induced endothelin-1 (ET-1) expression and subsequent cytotoxicity remain unclear. The present study aimed to investigate the hypothesis that H2S protects human umbilical vein endothelial cells (HUVECs) against AngII‑stimulated ET‑1 generation and subsequent cytotoxicity‑induced endoplasmic reticulum stress via the NF‑κB signaling pathway. The results of the present study demonstrated that AngII significantly upregulated the expression levels of ET‑1, glucose‑regulated protein 78, CCAAT‑enhancer‑binding protein homologous protein, phosphorylated (p)‑p65 and inducible nitric oxide synthase; stimulated nitric oxide production; suppressed the expression and activity of cystathionine-γ-lyase (CSE), a H2S synthetase; and decreased cell viability. Conversely, BQ788 (an ET‑1 receptor antagonist) exhibited an inhibitory effect on the AngII‑mediated suppression of CSE expression and activity in HUVECs. The effects of AngII were abrogated by sodium hydrosulfide (NaHS, an H2S donor), BQ788 or pyrrolidinedithiocarbamic acid (PDTC, an inhibitor of NF‑κB). Furthermore, pretreatment with NaHS or PDTC attenuated AngII‑induced apoptosis and cleaved caspase-12 generation. The pretreatment of HUVECs with BQ788 prior to AngII exposure mimicked the inhibitory effect of NaHS on the expression of p‑p65 induced by AngII. In conclusion, the present study provides evidence that exogenous H-2S attenuates AngII‑induced inflammation and cytotoxicity via inhibition of the ET‑1/NF‑κB signaling pathway in HUVECs.

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C. elegans Aging Is Modulated by Hydrogen Sulfide and the sulfhydrylase/cysteine Synthase cysl-2

Cited by 40 publications

References 57 publications

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response

Mitochondrial function in hypoxic ischemic injury and influence of aging

Hydrogen sulfide suppresses angiotensin II-stimulated endothelin-1 generation and subsequent cytotoxicity-induced endoplasmic reticulum stress in endothelial cells via NF-κB

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