Tadalafil Integrates Nitric Oxide-Hydrogen Sulfide Signaling to Inhibit High Glucose-induced Matrix Protein Synthesis in Podocytes

Lee, Hak‐Joo; Féliers, Denis; Mariappan, Meenalakshmi M.; Sataranatarajan, Kavithalakshmi; Choudhury, Goutam Ghosh; Gorin, Yves; Kasinath, Balakuntalam S.

doi:10.1074/jbc.m114.615377

Cited by 38 publications

(24 citation statements)

References 76 publications

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“…AKT and mTOR play critical role in regulating diverse cellular functions, including cell metabolism, growth, survival and migration. [28][29][30][31][32] mTOR phosphorylates and activates p70S6K on Thr 389. 31) Lee et al found that HG could inhibit mTORC1 activity.…”

Section: Discussionmentioning

confidence: 99%

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

Shen¹,

Fang²,

Guo³

et al. 2019

Biological & Pharmaceutical Bulletin

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MicroRNAs were involved in a wide range of biological processes of diabetic nephropathy (DN). It is reported that miR-15b-5p was downregulated in the patients with DN. However, the mechanisms underlying the regulatory effects of miR-15b-5p on patients with diabetes remain unclear. Thus, this study aimed to investigate the role of miR-15b-5p during high glucose (HG)-induced apoptosis in human kidney cells. Quantitative real-time (qRT)-PCR was used to detect the level of miR-15b-5p. CCK-8 assay, EdU staining assays and flow cytometry were used to detect cell proliferation, apoptosis respectively in vitro. In addition, Western blotting was used to determine active caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), phosphorylated (p)-AKT, p-mammalian target of rapamycin (mTOR), p-S6, p-c-Jun N terminal kinase (JNK), p-p38 and p-extracellular signal-regulated kinase (ERK) proteins levels. The expression of miR-15b-5p in patients with DN were dramatically decreased compared with health persons. Similarly, HG down-regulated the expression of miR-15b-5p in HK-2 cells. In contrast, miR-15b-5p mimics alleviated HG-induced apoptosis in HK-2 cells via decreasing the expressions of active caspase 3 and cleaved PARP. EdU detection further confirmed that miR-15b-5p mimics attenuated the anti-proliferation effect of HG in HK-2 cells. Furthermore, HGinduced Akt/mTOR pathway downregulation and JNK upregulation were markedly reversed by miR-15b-5p mimics in cells. The data suggested that miR-15b-5p mimics protects HK-2 cells from HG-induced apoptosis. The anti-apoptotic effects of miR-15b-5p may due to the activation of the Akt/mTOR pathway as well as inactivation of JNK. Taken together, miR-15b-5p might be a potential therapeutic target for the treatment of patients with DN.

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Section: Discussionmentioning

confidence: 99%

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

Shen¹,

Fang²,

Guo³

et al. 2019

Biological & Pharmaceutical Bulletin

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“…NO is more effective than TNF-α in mediating the killing of tumor cells by activated macrophages [91]. On the other hand, NO directly kills tumor cells: (1) NO acts on mitochondrial oxidoreductase, and tumor cells die due to energy metabolism disorders [92]; (2) NO combines with superoxide anion in cells to generate nitrogen/oxygen free radicals, resulting in genotoxicity and DNA damage [93]; (3) NO inhibits cell proliferation by inhibiting protein synthesis [94]; (4) NO activates the expression of p53 and induces apoptosis of tumor cells [94]; and (5) NO inhibits platelet aggregation and tumor metastasis [95]. In addition, a large number of studies have found that NO is also widely involved in the chemotherapy and immunotherapy of tumors, interacting with chemotherapy drugs and cytokines and affecting the efficacy of drugs against tumors [96].…”

Section: Oxidative Stress and Tumorsmentioning

confidence: 99%

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

Xie

Lei

et al. 2020

BioMed Research International

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Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.

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“…H2S is known to inhibit high glucose-induced protein synthesis in kidney podocytes. It was shown that treatment with tadalafil, a phosphodiesterase 5 inhibitor ameliorates high glucose stimulation of matrix proteins by generating H2S in podocytes through NO-H2S-AMPK axis [183]. Moreover, the anti-thrombotic efficacy of H2S involves the NOS-pathway and may be of preventive and therapeutic value for clinical disorders with increased risk of thrombotic events [184].…”

Section: A Crosstalk Between Nitric Oxide and Hydrogen Sulfidementioning

confidence: 99%

Functional and Molecular Insights of Hydrogen Sulfide Signaling and Protein Sulfhydration

Sen

2017

Journal of Molecular Biology

129

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Hydrogen sulfide (H2S) a novel gasotransmitter is endogenously synthesized by multiple enzymes that are differentially expressed in the peripheral tissues and central nervous systems. H2S regulates a wide range of physiological processes ranging from cardiovascular, neuronal, immune, respiratory, gastrointestinal, liver, and endocrine systems by influencing cellular signaling pathways and sulfhydration of target proteins. This review focuses on the recent progress made in H2S signaling that affects mechanistic and functional aspects of several biological processes such as autophagy, inflammation, proliferation and differentiation of stem cell, cell survival/death, and cellular metabolism under both physiological and pathological conditions. Moreover we highlighted the crosstalk between nitric oxide (NO) and H2S in several bilogical contexts.

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Tadalafil Integrates Nitric Oxide-Hydrogen Sulfide Signaling to Inhibit High Glucose-induced Matrix Protein Synthesis in Podocytes

Cited by 38 publications

References 76 publications

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

Functional and Molecular Insights of Hydrogen Sulfide Signaling and Protein Sulfhydration

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