Neuroprotective effect of S-allyl-l-cysteine derivatives against endoplasmic reticulum stress-induced cytotoxicity is independent of calpain inhibition

Imai, Toru; Kosuge, Yasuhiro; Saito, Hiroaki; Uchiyama, Taketo; Wada, Taira; Shimba, Shigeki; Ishige, Kumiko; Miyairi, Shinichi; Makishima, Makoto; Ito, Yoshihisa

doi:10.1016/j.jphs.2016.03.004

Cited by 14 publications

(7 citation statements)

References 12 publications

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“…However, in other studies, SAC (as opposed to DATS) did not exhibit significant inhibitory effects on inflammatory mediator production in LPS-stimulated microglial cells in vitro (Ho and Su, 2014). Although SAC clearly has beneficial effects in many models of disease (ranging from diabetic complications to hypertension) (Park et al, 2014;Denzer et al, 2016;Imai et al, 2016;Uzun et al, 2016;Brahmanaidu et al, 2017;Kattaia et al, 2017), it is likely that its pharmacological effects encompass multiple additional actions beyond H 2 S donation.…”

Section: Natural H 2 S Donorsmentioning

confidence: 86%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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Over the last decade, hydrogen sulfide (HS) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, HS is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. HS levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of HS, either based on HS donation or inhibition of HS biosynthesis. HS donation can be achieved through the inhalation of HS gas and/or the parenteral or enteral administration of so-called fast-releasing HS donors (salts of HS such as NaHS and NaS) or slow-releasing HS donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated HS release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with HS-donating groups (the most advanced compound in clinical trials is ATB-346, an HS-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of HS synthesis, there are now several small molecule compounds targeting each of the three HS-producing enzymes cystathionine--synthase (CBS), cystathionine--lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous HS production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known HS donors and HS biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.

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Section: Natural H 2 S Donorsmentioning

confidence: 86%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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“…Among these are S-methyl-L-cysteine (SMC), S-ethyl-L-cysteine (SEC) and S-propyl-L-cysteine (SPC), three typical hydrophilic cysteine-containing compounds naturally found in garlic (27). More recently, we synthesized various structurally related derivatives of SAC and examined their neuroprotective effects in a model of ER stress based on tunicamycin-induced neurotoxicity in rat cultured hippocampal neurons (28) Cultured hippocampal neurons were treated with tunicamycin (10 µg/ml) in the absence or presence of 1 µM of a SAC derivative. These experiments demonstrated that the neuroprotective effects of the side-chain substituted SAC derivatives, SEC and SPC, against ER stress-induced cytotoxicity were more potent than those of SAC (Fig.…”

Section: Analogs Of Sacmentioning

confidence: 99%

Neuroprotective mechanisms of S-allyl-L-cysteine in neurological disease (Review)

Kosuge

2019

Exp Ther Med

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S-allyl-L-cysteine (SAC) is a sulfur-containing amino acid present in garlic and exhibits a wide range of biological activities such as antioxidant, anti-inflammatory, and anticancer agent. An earlier study demonstrated that SAC ameliorates oxidative damage in a model of experimental stroke. However, the antioxidant property of SAC does not suffice to explain its beneficial effects in terms of the underlying mechanisms. Endoplasmic reticulum (ER) stress and ER stress-induced cell death have been shown to be involved in various neurological diseases such as brain ischemia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. We have previously demonstrated that SAC exerts significant protective effects against ER stress-induced neurotoxicity in cultured rat hippocampal neurons and organotypic hippocampal slice cultures. Recently, we demonstrated that these results are due to the direct suppression of calpain activity via the binding of SAC to this enzyme's Ca 2+-binding domain. We also found that the protective effects of the side-chain-modified SAC derivatives, S-ethyl-L-cysteine (SEC) and S-propyl-L-cysteine (SPC), against ER stress-induced neurotoxicity were more potent than those of SAC in cultured rat hippocampal neurons. In addition, SAC, SEC and SPC have been shown to decrease the production of amyloid-β peptide in the brains of mice with D-galactose-induced aging. These three hydrophilic cysteine-containing compounds have also been shown to exert neuroprotective effects against dopaminergic neuron injury in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this review, we aim to provide a current overview of the protective actions of SAC and the SAC-related compounds, SEC and SPC, in neurodegenerative disease and discuss the promise of SAC as a prototype for developing novel therapeutic drugs for neurological diseases. Contents 1. Introduction 2. Protective effects of SAC against neuronal death due to ER stress 3. Calpain is a probable target molecule for SAC 4. Analogs of SAC 5. Conclusions and future perspectives

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“…Few synthetic derivatives of S-allyll-cysteine (SAC) also showed the same effect. Among them, S-propyl-l-cysteine (SPC) was the strongest one [33].…”

Section: Neuroprotective Effectmentioning

confidence: 99%

Bioactivities of Allicin and Related Organosulfur Compounds from Garlic: Overview of the Literature Since 2010

Mandal¹,

Das²,

Dey³

et al. 2019

Egypt. J. Chem.

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T HE medical values of garlic, a traditionally used allium vegetable, were recognized as early as 3000 BC. Allicin, one of the major organosulfur compounds present in garlic, is associated with a wide variety of benificial activities like anticancer, anti-inflammatory, antiarthritic, antimicrobial, anti-diabetic, cholesterol-lowering, the potential to lower cardiovascular disorders, ameliorating neuron functions, etc. In this article, we have reviewed biological activities of allicin and related organosulfur compounds since the year 2010, using various scientific websites like Pub med, Google Scholar, Science Direct etc. Our literature review has highlighted many organo sulphur components of garlic and their possible mechanisms in curing different diseases. The information provided in this review will provide strategies for efficient organosulfur-based treatments of several diseases in future. Further research efforts are needed for a clear understanding of the interconnection between these functional components and various chronic diseases.

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Neuroprotective effect of S-allyl-l-cysteine derivatives against endoplasmic reticulum stress-induced cytotoxicity is independent of calpain inhibition

Cited by 14 publications

References 12 publications

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

Neuroprotective mechanisms of S-allyl-L-cysteine in neurological disease (Review)

Bioactivities of Allicin and Related Organosulfur Compounds from Garlic: Overview of the Literature Since 2010

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Neuroprotective effect of S-allyl-l-cysteine derivatives against endoplasmic reticulum stress-induced cytotoxicity is independent of calpain inhibition

Cited by 14 publications

References 12 publications

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

Neuroprotective mechanisms of S-allyl-L-cysteine in neurological disease (Review)

Bioactivities of Allicin and Related Organosulfur Compounds from Garlic: Overview of the Literature Since 2010

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Product

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International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors