Sodium tanshinone IIA sulfonate inhibits hypoxia-induced enhancement of SOCE in pulmonary arterial smooth muscle cells via the PKG-PPAR-γ signaling axis
Copyright © 2016 the American Physiological Society..
Our laboratory previously showed that sodium tanshinone IIA sulfonate (STS) inhibited store-operated Ca(2+) entry (SOCE) through store-operated Ca(2+) channels (SOCC) via downregulating the expression of transient receptor potential canonical proteins (TRPC), which contribute to the formation of SOCC (Wang J, Jiang Q, Wan L, Yang K, Zhang Y, Chen Y, Wang E, Lai N, Zhao L, Jiang H, Sun Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 48: 125-134, 2013). The detailed molecular mechanisms by which STS inhibits SOCE and downregulates TRPC, however, remain largely unknown. We have previously shown that, under hypoxic conditions, inhibition of protein kinase G (PKG) and peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling axis results in the upregulation of TRPC (Wang J, Yang K, Xu L, Zhang Y, Lai N, Jiang H, Zhang Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 49: 231-240, 2013). This suggests that strategies targeting the restoration of this signaling pathway may be an effective treatment strategy for pulmonary hypertension. In this study, our results demonstrated that STS treatment can effectively prevent the hypoxia-mediated inhibition of the PKG-PPAR-γ signaling axis in rat distal pulmonary arterial smooth muscle cells (PASMCs) and distal pulmonary arteries. These effects of STS treatment were blocked by pharmacological inhibition or specific small interfering RNA knockdown of either PKG or PPAR-γ. Moreover, targeted PPAR-γ agonist markedly enhanced the beneficial effects of STS. These results comprehensively suggest that STS treatment can prevent hypoxia-mediated increases in intracellular calcium homeostasis and cell proliferation, by targeting and restoring the hypoxia-inhibited PKG-PPAR-γ signaling pathway in PASMCs.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:311 |
|---|---|
| Enthalten in: |
American journal of physiology. Cell physiology - 311(2016), 1 vom: 01. Juli, Seite C136-49 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jiang, Qian [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.06.2017 Date Revised 24.07.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1152/ajpcell.00252.2015 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM260489921 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM260489921 | ||
| 003 | DE-627 | ||
| 005 | 20231224193519.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1152/ajpcell.00252.2015 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0868.xml |
| 035 | |a (DE-627)NLM260489921 | ||
| 035 | |a (NLM)27194472 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jiang, Qian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sodium tanshinone IIA sulfonate inhibits hypoxia-induced enhancement of SOCE in pulmonary arterial smooth muscle cells via the PKG-PPAR-γ signaling axis |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.06.2017 | ||
| 500 | |a Date Revised 24.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 the American Physiological Society. | ||
| 520 | |a Our laboratory previously showed that sodium tanshinone IIA sulfonate (STS) inhibited store-operated Ca(2+) entry (SOCE) through store-operated Ca(2+) channels (SOCC) via downregulating the expression of transient receptor potential canonical proteins (TRPC), which contribute to the formation of SOCC (Wang J, Jiang Q, Wan L, Yang K, Zhang Y, Chen Y, Wang E, Lai N, Zhao L, Jiang H, Sun Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 48: 125-134, 2013). The detailed molecular mechanisms by which STS inhibits SOCE and downregulates TRPC, however, remain largely unknown. We have previously shown that, under hypoxic conditions, inhibition of protein kinase G (PKG) and peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling axis results in the upregulation of TRPC (Wang J, Yang K, Xu L, Zhang Y, Lai N, Jiang H, Zhang Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 49: 231-240, 2013). This suggests that strategies targeting the restoration of this signaling pathway may be an effective treatment strategy for pulmonary hypertension. In this study, our results demonstrated that STS treatment can effectively prevent the hypoxia-mediated inhibition of the PKG-PPAR-γ signaling axis in rat distal pulmonary arterial smooth muscle cells (PASMCs) and distal pulmonary arteries. These effects of STS treatment were blocked by pharmacological inhibition or specific small interfering RNA knockdown of either PKG or PPAR-γ. Moreover, targeted PPAR-γ agonist markedly enhanced the beneficial effects of STS. These results comprehensively suggest that STS treatment can prevent hypoxia-mediated increases in intracellular calcium homeostasis and cell proliferation, by targeting and restoring the hypoxia-inhibited PKG-PPAR-γ signaling pathway in PASMCs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a PKG | |
| 650 | 4 | |a PPAR-γ | |
| 650 | 4 | |a SOCE | |
| 650 | 4 | |a STS | |
| 650 | 4 | |a TRPC | |
| 650 | 7 | |a PPAR gamma |2 NLM | |
| 650 | 7 | |a PPAR gamma, rat |2 NLM | |
| 650 | 7 | |a Phenanthrenes |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a TRPC Cation Channels |2 NLM | |
| 650 | 7 | |a Trpc6 protein, rat |2 NLM | |
| 650 | 7 | |a transient receptor potential cation channel, subfamily C, member 1 |2 NLM | |
| 650 | 7 | |a tanshinone II A sodium sulfonate |2 NLM | |
| 650 | 7 | |a 69659-80-9 |2 NLM | |
| 650 | 7 | |a Cyclic GMP-Dependent Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.12 |2 NLM | |
| 700 | 1 | |a Lu, Wenju |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Hadadi, Cyrus |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuqin |e verfasserin |4 aut | |
| 700 | 1 | |a Yun, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Meichan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Haiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Jason X-J |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Dejun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of physiology. Cell physiology |d 2000 |g 311(2016), 1 vom: 01. Juli, Seite C136-49 |w (DE-627)NLM105734659 |x 1522-1563 |7 nnns |
| 773 | 1 | 8 | |g volume:311 |g year:2016 |g number:1 |g day:01 |g month:07 |g pages:C136-49 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1152/ajpcell.00252.2015 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 311 |j 2016 |e 1 |b 01 |c 07 |h C136-49 | ||