Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

Fukami, Kazuki; Sekiguchi, Fumiko; Asano, Erina; Yoshida, Shigeru; Kawabata, Atsufumi

doi:10.1016/j.bcp.2015.08.005

Cited by 30 publications

(27 citation statements)

References 55 publications

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“…In the nociceptor neurons, H 2 S enhances the function of Ca v 3.2 T-type Ca 2+ channels [8][9][10][11][12] and TRPA1 channels [13,14] , leading to the neuronal excitation and then pain sensation or hyperalgesia/allodynia [3,7,15] . We have also shown that the acceleration of Ca v 3.2 channel activity by exogenous H 2 S causes neuritogenesis and neuronal differentiation in NG108-15 cells [9,10,16] , and that the endogenous H 2 S/ Ca v 3.2 pathway regulates secretory function in the neuroendocrine-like differentiated human prostate cancer LNCaP cells [17] . Here, we thus focus on the roles of Ca v 3.2 T-type Ca 2+ channels and H 2 S in pain processing, neuronal differentiation and neuroendocrine secretion.…”

mentioning

confidence: 99%

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Fukami

Sekiguchi²,

Kawabata³

2016

Pharmacology

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Background: Hydrogen sulfide (H₂S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H₂S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Ca_v3.2 T-type Ca²⁺ channels mediate some of the biological activity of H₂S, we focus on the role of the H₂S/Ca_v3.2 pathway in regulating the neuronal and neuroendocrine function. Summary: In the neuronal system, H₂S regulates the activity of various ion channels including Ca_v3.2. Exogenous and endogenous H₂S enhances the Ca_v3.2 channel activity, promoting somatic and visceral pain signaling. The H₂S/Ca_v3.2 pathway also facilitates neuritogenesis or neuronal differentiation. Interestingly, endogenous H₂S formed by CSE regulates secretory function by enhancing Ca_v3.2 channel activity in neuroendocrine-differentiated prostate cancer cells or carotid glomus cells. Key Messages: The H₂S/Ca_v3.2 pathway may serve as therapeutic targets for treatment of intractable pain, neuronal injury, androgen-independent prostate cancer, cardiovascular diseases, etc.

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confidence: 99%

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Fukami

Sekiguchi²,

Kawabata³

2016

Pharmacology

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“…We used the polyclonal antibody against rat CSE in the present study, because we have accumulated evidence that this antibody specifically recognizes not only rat and mouse CSE, 15,16) but also human CSE. 17) On the other hand, we used the monoclonal antibody against human CBS, the specificity of which was confirmed in our recent study. 17) After washing the primary antibodies, the membrane was then incubated with horseradish peroxidase (HRP)-conjugated anti-rabbit or anti-mouse antibodies (Cell Signaling Technol., Beverly, MA, U.S.A.).…”

Section: Methodsmentioning

confidence: 73%

“…17) On the other hand, we used the monoclonal antibody against human CBS, the specificity of which was confirmed in our recent study. 17) After washing the primary antibodies, the membrane was then incubated with horseradish peroxidase (HRP)-conjugated anti-rabbit or anti-mouse antibodies (Cell Signaling Technol., Beverly, MA, U.S.A.). Immunolabelled proteins were visualized by ChemiLumi One Super (Nacalai Tesque, Kyoto, Japan).…”

Section: Methodsmentioning

confidence: 73%

Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells

Sekiguchi

Sekimoto

Ogura

et al. 2016

Biological & Pharmaceutical Bulletin

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Hydrogen sulfide (H 2 S), the third gasotransmitter, is endogenously generated by certain H 2 S synthesizing enzymes, including cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H 2 S affects the proliferation of cancer cells, although the effects of H 2 S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H 2 S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and β-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H 2 S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H 2 S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions.

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“…It was shown that T-type calcium channels, due to their combined inactivation and activation properties, participate in basal calcium entry at a resting membrane potential of -40 mV in LNCaP prostate cells [72]. The overexpression of Cav3.2 channels was shown to be mediated by a transcriptional mechanism in response to the activation of adenylyl/PKA-Egr-1 pathway [52,73], to androgen depletion [52] or to sodium butyrate exposition [74]. On the opposite, it was shown that interkeukin 6 (IL6), which also promotes NE differentiation, increases Cav3.2 channels through a posttranscriptional mechanism [75].…”

Section: Expression Of Voltage-dependent Calcium Channelsmentioning

confidence: 99%

“…Cav3.2 expression and activity are therefore responsible for PAP secretion in NE prostate cancer cells [86]. In addition, it has been demonstrated that Cav3.2 channels are activated by hydrogen sulfide (H 2 S) which is produced by an overexpression of cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) during NE differentiation of LNCaP cells [73]. This in turn leads to increased se-cretory function of NE cells.…”

Section: Role Of T-type Calcium Channels In Secretionmentioning

confidence: 99%

Expression and Role of T-type Calcium Channels during Neuroendocrine Differentiation

Warnier¹,

Gackière²,

Roudbaraki³

et al. 2017

J Cell Signal

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Neuroendocrine cells release their secretion into the extracellular environment through calcium-dependent signalling pathways. These cells share common morphological and molecular features such as the expression of specific biomarkers, neurite outgrowth and dense core secretory granules. In order to elucidate the signalling pathways leading from undifferentiated to differentiated neuroendocrine cells, the role of voltage-dependent calcium channels, central actors in the excitation-secretion coupling, has been comprehensively investigated. T-type calcium channels appear to belong to the most important ion channel family involved in the neuroendocrine differentiation process. They could also participate in the development of neuroendocrine tumours.

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Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

Cited by 30 publications

References 55 publications

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells

Expression and Role of T-type Calcium Channels during Neuroendocrine Differentiation

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