Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner

AbstractHydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSnH). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions and interventions known to modulate H2S production. We hypothesize that dietary restriction (DR), which increases lifespan and can boost H2S production, expands tissue-specific persulfidomes. Here, we find protein persulfidation enriched in liver, kidney, muscle, and brain but decreased in heart of young and aged male mice under two forms of DR, with DR promoting persulfidation in numerous metabolic and aging-related pathways. Mice lacking cystathionine γ-lyase (CGL) have overall decreased tissue protein persulfidation numbers and fail to functionally augment persulfidomes in response to DR, predominantly in kidney, muscle, and brain. Here, we define tissue- and CGL-dependent persulfidomes and how diet transforms their makeup, underscoring the breadth for DR and H2S to impact biological processes and organismal health.

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Dietary restriction transforms the protein sulfhydrome in a tissue-specific and cystathionine γ-lyase-dependent manner

10.1101/869271 ◽

2019 ◽

Cited By ~ 1

Author(s):

Nazmin Bithi ◽

Christopher Link ◽

Rui Wang ◽

Belinda Willard ◽

Christopher Hine

Keyword(s):

Hydrogen Sulfide ◽

Dietary Restriction ◽

Active Metabolite ◽

Dependent Manner ◽

Biological Processes ◽

Tissue Specific ◽

Downstream Signaling ◽

Redox Active ◽

Associated Functions ◽

Liver And Kidney

AbstractHydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein sulfhydration (R-SSnH). Despite the known importance of sulfhydration on relatively few identified proteins, tissue-specific sulfhydrome profiles and their associated functions are not well characterized, specifically under conditions known to modulate H2S production. We hypothesized that dietary restriction (DR), which increases lifespan and boosts endogenous H2S production, expands functional tissue-specific sulfhydromes. Here, we found that 50% DR enriched total sulfhydrated proteins in liver, kidney, muscle, and brain but decreased these in heart of adult male mice. DR promoted sulfhydration in numerous metabolic and aging-related pathways. Mice lacking the H2S producing enzyme cystathionine γ-lyase (CGL) had decreased liver and kidney protein sulfhydration and failed to functionally augment their sulfhydrome in response to DR. Overall, we defined tissue- and CGL-dependent sulfhydromes and how diet transforms their makeup, underscoring the breadth for DR and H2S to impact biological processes and organismal health.One Sentence SummaryDietary restriction altered the tissue-specific enrichment of sulfhydrated proteins and their downstream signaling pathways in liver, kidney, skeletal muscle, brain, heart, and plasma that was partly dependent on the hydrogen sulfide producing enzyme cystathionine γ-lyase.

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The effect of deer antler from East Kalimantan to increase trabecular bone density and calcium levels in serum on osteoporotic mice

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0140 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Retno Widyowati ◽

Suciati Suciati ◽

Dewi Melani Haryadi ◽

Hsin-I Chang ◽

IPG Ngurah Suryawan ◽

...

Keyword(s):

Bone Density ◽

Trabecular Bone ◽

Aqueous Extract ◽

Dependent Manner ◽

Aqueous Extracts ◽

Trabecular Bone Density ◽

Male Mice ◽

Deer Antler ◽

East Kalimantan ◽

Dose Dependent

Abstract Objectives Glucocorticoid-induced osteoporosis (dexamethasone) is a primary cause of secondary osteoporosis by the decreasing formation and increasing resorption activities. Previously, the in vitro study showed that 70% ethanol and aqueous extract of deer antler have increased alkaline phosphatase in osteoblast cell that known as marker of bone formation. The mind of this study is to analyze the effect of deer antlers in increasing the bone trabecular density of osteoporosis-induced male mice. Methods This study used a post-test control group design. A total of 54 healthy male mice were randomly divided to nine groups, i.e., healthy control, osteoporotic, positive control, 70% ethanol (4, 8, and 12 mg/kg BW), and aqueous extracts (4, 8, and 12 mg/kg BW) of deer antler groups. All of the interventions were given 1 mL of test sample for 4 weeks orally. The bone densities were determined using histomorphometry by Image J and Adobe Photoshop. The statistical data were performed using SPSS 23 and statistical significance was set at p<0.05. Results The results showed that alendronate group, 70% ethanol, and aqueous extract groups increased bone density and calcium levels in serum (p<0.05) compared to osteoporotic group in dose dependent manner. It indicated that 70% ethanol and aqueous extract of deer antler stimulating bone turnover and aqueous extract showed the highest. Conclusions Dexamethasone induction for 4 weeks caused osteoporotic mice and the administration of 70% ethanol and aqueous extracts of deer antler from East Kalimantan increased trabecular bone density and calcium levels in dose dependent manner.

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Tissue-specific distribution of cross-linked somatostatin receptor proteins in the rat

Biochemical Journal ◽

10.1042/bj2820339 ◽

1992 ◽

Vol 282 (2) ◽

pp. 339-344 ◽

Cited By ~ 3

Author(s):

C B Srikant ◽

K K Murthy ◽

Y C Patel

Keyword(s):

Exocrine Pancreas ◽

Receptor Protein ◽

Cross Linking ◽

Molecular Heterogeneity ◽

Dependent Manner ◽

Tissue Specific ◽

Receptor Proteins ◽

Specific Distribution ◽

A Minor ◽

The Brain

Pharmacological studies have suggested that the somatostatin (SS) receptor is heterogeneous and exhibits SS-14-and SS-28-selective subtypes. Whether such subtypes arise from molecular heterogeneity of the receptor protein has not been definitively established. Previous reports characterizing the molecular properties of the SS receptor by the cross-linking approach have yielded divergent size estimates ranging from 27 kDa to 200 kDa. In order to resolve this discrepancy, as well as to determine whether SS-14 and SS-28 interact with specific receptor proteins, we have cross-linked radioiodinated derivatives of [125I-Tyr11]SS-14 (T*-SS-14) and [Leu8,D-Trp22,125I-Tyr25]SS-28 (LTT*-SS-28) to membrane SS receptors in rat brain, pituitary, exocrine pancreas and adrenal cortex using a number of chemical and photoaffinity cross-linking agents. The labelled cross-linked receptor proteins were analysed by SDS/PAGE under reducing conditions followed by autoradiography. Our findings indicate that the pattern of specifically labelled cross-linked SS receptor proteins is sensitive to the concentration of chemical cross-linking agents such as disuccinimidyl suberate and dithiobis-(succinimidyl propionate). Labelled high-molecular-mass complexes of cross-linked receptor-ligand proteins were observed only when high concentrations of these cross-linkers were employed. Using optimized low concentrations of cross-linkers, however, two major labelled bands of 58 +/- 3 kDa and 27 +/- 2 kDa were detected. These two bands were identified as specifically labelled SS receptor proteins subsequent to cross-linking with a number of photoaffinity cross-linking agents as well. We demonstrate here that the 58 kDa protein is the major SS receptor protein in the rat pituitary, adrenal and exocrine pancreas, whereas the 27 kDa moiety represents the principal form in the brain. Additionally, the presence of a minor specifically labelled band of 32 kDa was detected uniquely in the brain, and a minor labelled protein of 42 kDa was observed in the pancreas. The labelling pattern obtained with LTT*-SS-28 was identical to that observed with T*-SS-14. Labelling of the 27 kDa band by either ligand was inhibited by SS-14 and SS-28 in a dose-dependent manner. Densitometric quantification showed that SS-14 exhibited greater than 2-fold greater potency than SS-28 for inhibiting the labelling of the 27 kDa species. These findings emphasize the need for careful interpretation of cross-linking data obtained for SS receptors, and provide evidence for molecular heterogeneity and for a tissue-specific distribution of the two principal SS receptor proteins.

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Dichotomous roles of TGF-β in human cancer

Biochemical Society Transactions ◽

10.1042/bst20160065 ◽

2016 ◽

Vol 44 (5) ◽

pp. 1441-1454 ◽

Cited By ~ 44

Author(s):

Jennifer J. Huang ◽

Gerard C. Blobe

Keyword(s):

Signaling Pathway ◽

Cancer Progression ◽

Transforming Growth Factor ◽

Human Cancer ◽

Transforming Growth Factor Β ◽

Dependent Manner ◽

Biological Processes ◽

Cellular Homeostasis ◽

Angiogenic Therapy ◽

Promising Strategy

Transforming growth factor-β (TGF-β) mediates numerous biological processes, including embryonic development and the maintenance of cellular homeostasis in a context-dependent manner. Consistent with its central role in maintaining cellular homeostasis, inhibition of TGF-β signaling results in disruption of normal homeostatic processes and subsequent carcinogenesis, defining the TGF-β signaling pathway as a tumor suppressor. However, once carcinogenesis is initiated, the TGF-β signaling pathway promotes cancer progression. This dichotomous function of the TGF-β signaling pathway is mediated through altering effects on both the cancer cells, by inducing apoptosis and inhibiting proliferation, and the tumor microenvironment, by promoting angiogenesis and inhibiting immunosurveillance. Current studies support inhibition of TGF-β signaling either alone, or in conjunction with anti-angiogenic therapy or immunotherapy as a promising strategy for the treatment of human cancers.

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Pygo1 regulates pathological cardiac hypertrophy via a β-catenin-dependent mechanism

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00538.2020 ◽

2021 ◽

Author(s):

Li Lin ◽

Wei Xu ◽

Yongqing Li ◽

Ping Zhu ◽

Wuzhou Yuan ◽

...

Keyword(s):

Cardiac Hypertrophy ◽

Cardiac Tissue ◽

Heart Weight ◽

Dependent Manner ◽

Tissue Specific ◽

Cardiac Tissues ◽

Pathological Cardiac Hypertrophy ◽

Interaction Factor ◽

Myocardial Remodelling

Wnt/β-catenin signalling plays a key role in pathological cardiac remodelling in adults. The identification of a tissue-specific Wnt/β-catenin interaction factor may realise a tissue-specific clinical targeting strategy. Drosophila Pygo codes for the core interaction factor of Wnt/β-catenin. Two Pygo homologs, Pygo1 and Pygo2, have been identified in mammals. Different from the ubiquitous expression profile of Pygo2, Pygo1is enriched in cardiac tissue. However, the role of Pygo1 in mammalian cardiac disease remains unelucidated. Here, we found that Pygo1 was upregulated in human cardiac tissues with pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy accompanied by declined cardiac function, increased heart weight/body weight and heart weight/tibial length ratios and increased cell size. The canonical β-catenin/T-cell transcription factor 4 complex was abundant in Pygo1-overexpressingtransgenic(Pygo1-TG) cardiac tissue,and the downstream genes of Wnt signaling, i.e., Axin2, Ephb3, and C-myc, were upregulated. A tail vein injection of β-catenin inhibitor effectively rescued the phenotype of cardiac failure and pathological myocardial remodelling in Pygo1-TG mice. Furthermore, in vivo downregulated pygo1 during cardiac hypertrophic condition antagonized agonist-induced cardiac hypertrophy. Therefore, our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/β-catenin-dependent manner, which may provide new clues for a tissue-specific clinical treatment targeting this pathway.

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Two novel first exons in the prolactin receptor gene are transcribed in a tissue-specific and sexual maturation-dependent manner to encode multiple 5′-truncated transcripts in the testis of the chicken

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression ◽

10.1016/s0167-4781(00)00019-1 ◽

2000 ◽

Vol 1491 (1-3) ◽

pp. 279-284 ◽

Cited By ~ 11

Author(s):

Minoru Tanaka ◽

Ichiro Yamamoto ◽

Yukinobu Hayashida ◽

Nobuhiro Nakao ◽

Takeshi Ohkubo ◽

...

Keyword(s):

Sexual Maturation ◽

Receptor Gene ◽

Prolactin Receptor ◽

Dependent Manner ◽

Tissue Specific ◽

Prolactin Receptor Gene

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Human glucagon gene promoter sequences regulating tissue-specific versus nutrient-regulated gene expression

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00215.2001 ◽

2002 ◽

Vol 282 (1) ◽

pp. R173-R183 ◽

Cited By ~ 23

Author(s):

Min Nian ◽

Jun Gu ◽

David M. Irwin ◽

Daniel J. Drucker

Keyword(s):

Gene Expression ◽

Gene Promoter ◽

Regulatory Sequences ◽

Dependent Manner ◽

Specific Expression ◽

Tissue Specific ◽

High Fiber ◽

Fiber Diet ◽

Regulated Gene Expression

The glucagon-like peptides (GLPs) are synthesized and secreted in a nutrient-dependent manner in rodents; however, the factors regulating human GLP-1 and GLP-2 biosynthesis remain unclear. To understand how nutrients regulate human proglucagon gene expression, we studied the expression of a human proglucagon promoter-growth hormone (GH) transgene in 1.6 human glucagon-GH transgenic mice. Fasting-refeeding significantly decreased and increased the levels of circulating mouse insulin and transgene-derived hGH ( P < 0.05 fasting vs. refeeding) and decreased and upregulated, respectively, the levels of endogenous mouse proglucagon RNA in the ileum but not in the jejunum or colon. High-fiber feeding significantly increased the levels of glucose-stimulated circulating hGH and upregulated levels of mouse intestinal proglucagon gene expression in the jejunum, ileum, and colon ( P < 0.05, 0 vs. 30% fiber diet). In contrast, neither fasting-refeeding nor a high-fiber diet upregulated the expression of the human proglucagon promoter-hGH transgene. These findings demonstrate that human proglucagon gene regulatory sequences specifying tissue-specific expression in gut endocrine cells are not sufficient for recognition of energy-derived signals regulating murine glucagon gene expression in enteroendocrine cells in vivo.

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Hypoxia induces a time- and tissue-specific response that elicits intertissue circadian clock misalignment

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1914112117 ◽

2019 ◽

Vol 117 (1) ◽

pp. 779-786 ◽

Cited By ~ 10

Author(s):

Gal Manella ◽

Rona Aviram ◽

Nityanand Bolshette ◽

Sapir Muvkadi ◽

Marina Golik ◽

...

Keyword(s):

Circadian Clock ◽

Ex Vivo ◽

Acute Hypoxia ◽

Time Of Day ◽

Chronic Obstructive ◽

Specific Response ◽

Dependent Manner ◽

Tissue Specific ◽

Circadian Misalignment ◽

Obstructive Sleep

The occurrence and sequelae of disorders that lead to hypoxic spells such as asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea (OSA) exhibit daily variance. This prompted us to examine the interaction between the hypoxic response and the circadian clock in vivo. We found that the global transcriptional response to acute hypoxia is tissue-specific and time-of-day–dependent. In particular, clock components differentially responded at the transcriptional and posttranscriptional level, and these responses depended on an intact circadian clock. Importantly, exposure to hypoxia phase-shifted clocks in a tissue-dependent manner led to intertissue circadian clock misalignment. This differential response relied on the intrinsic properties of each tissue and could be recapitulated ex vivo. Notably, circadian misalignment was also elicited by intermittent hypoxia, a widely used model for OSA. Given that phase coherence between circadian clocks is considered favorable, we propose that hypoxia leads to circadian misalignment, contributing to the pathophysiology of OSA and potentially other diseases that involve hypoxia.

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