Heparin recovers AT1 receptor and its intracellular signal transduction in cultured vascular smooth muscle cells

Hashimoto, Tatsuo; Kihara, Minoru; Satô, Keiko; Imai, Nozomi; Tanaka, Yutaka; Sakai, Masashi; Tamura, Kouichi; Hirawa, Nobuhito; Toya, Yoshiyuki; Kitamura, Hitoshi; Umemura, Satoshi

doi:10.1016/j.febslet.2004.11.093

Cited by 15 publications

(16 citation statements)

References 19 publications

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“…Deletion of Gq/11 in adult mouse VSMCs results in abolished vasoconstrictive responses, lower basal blood pressure, and reduced salt-induced hypertension (25). Importantly, we found that force generation of IP 3 R-deficient aortas was reduced in response to multiple vasoconstrictors, such as PE, U46619, 5-HT, and ET1, suggesting that IP 3 R-mediated Ca 2+ release plays an important role in regulating vascular contraction following activation of GPCR, which is consistent with previous studies using the IP 3 R blockers heparin, 2-APB, or Xestospongin (30)(31)(32)(33). Our results also suggested that both IP 3 R-dependent and IP 3 R-independent pathways could contribute to Gq/11-mediated regulation of vascular contraction, since deletion of Gq/11 has much more efficacy in reducing vasoconstrictive responses than deletion of IP 3 Rs.…”

Section: +supporting

confidence: 80%

IP3 receptors regulate vascular smooth muscle contractility and hypertension

et al. 2016

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Section: +supporting

confidence: 80%

IP3 receptors regulate vascular smooth muscle contractility and hypertension

et al. 2016

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“…Real-time quantitative RT-PCR was also performed to examine the effect of salt depletion on MAK-V/Hunk and AT1 receptor mRNA expression in the mouse kidney, as described previously (13). Briefly, PCR was performed by incubating the RT product with the TaqMan Universal PCR Master Mix and designed TaqMan probe (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Expression of MAK-V/Hunk in renal distal tubules and its possible involvement in proliferative suppression

Sakai¹,

Tamura²,

Tsurumi³

et al. 2007

American Journal of Physiology-Renal Physiology

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MAK-V/Hunk is an SNF1-related serine/threonine kinase which was previously shown to be highly expressed in the mammary gland and central nervous system. In this study, we found MAK-V/Hunk is abundantly and specifically expressed in the thick ascending limbs and distal convoluted tubules (DCT) of the kidney from the embryonic stage to the adult stage. We demonstrated that dietary salt depletion significantly enhances renal MAK-V/Hunk mRNA levels compared with a normal-salt diet. To analyze the possible renal cellular function of this kinase, we employed mouse distal convoluted tubule (mDCT) cells. The results of reverse transcriptase-polymerase chain reaction and Western blot analysis revealed that MAK-V/Hunk is expressed endogenously in mDCT cells. Overexpression of MAK-V/Hunk by adenoviral gene transfer significantly inhibited the ANG II-induced stimulation of c-fos gene transcription and suppressed the ANG II-mediated increases in transforming growth factor-beta production into the medium. This phenomenon was accompanied by inhibition of ANG II-induced activation of BrdU incorporation. On the other hand, the MAK-V/Hunk knockdown by siRNA activated the ANG II-induced c-fos gene expression. In the consecutive sections stained for MAK-V/Hunk and AT(1) receptor, MAK-V/Hunk-immunopositive distal tubules expressed the AT(1) receptor. This is the first report on the intrarenal localization of MAK-V/Hunk and its cellular function in renal tubular cells.

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“…Vascular smooth muscle cells (VSMC) from the thoracic aorta of 4-week-old male Wistar rats were prepared by the explant method. 32 And human embryonic kidney (HEK) 293 cells were provided by ATCC (CRL-1573). These cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), penicillin (100 U/ml), and streptomycin (100 U/ml) (all obtained from Invitrogen (ON, Canada)) at 371C in a humidified atmosphere of 95% air and 5% CO 2 .…”

Section: Materials and Methods Agents And Cell Culturementioning

confidence: 99%

“…Relative expression levels were expressed by a comparative threshold cycle (C T ) method as described previously. 32 Cell Growth Assay Cells (2.5 Â 10 4 cells/well) were plated on 96-well plates in DMEM with 10% FBS. After a 24-h incubation with 10% FBS, the cells were serum starved for 24 h, and then pretreated with CV11974 (4 Â 10 À5 mol/l) for 24 h and treated with various concentrations of AII (10 À6 , 10 À8 , 10 À10 , and 10 À12 mol/l) for 24 h. After a 2-day treatment, the net number of viable cells was determined using a water-soluble…”

Section: Western Blot Analysismentioning

confidence: 99%

Roles for host and tumor angiotensin II type 1 receptor in tumor growth and tumor-associated angiogenesis

Imai

Hashimoto

Kihara

et al. 2007

Laboratory Investigation

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Angiotensin II (AII) is a multifunctional bioactive peptide, and host renin-angiotensin system (RAS) is closely associated with tumor growth. Recent reports have described that AII is a proangiogenic growth factor, and that Angiotensin II type 1 (AT1) receptor antagonists reduce tumor growth and tumor-associated angiogenesis. In this paper, we investigated the participation of AT1 receptor-signaling in cancer progression using murine Lewis lung carcinoma (LLC) cells, which express AT1 receptor, and AT1a receptor gene-deficient (AT1aÀ/À) mice. When LLC cells were implanted subcutaneously into wild-type (WT) mice, developed tumors showed intensive angiogenesis with an induction of vascular endothelial growth factor (VEGF) a. Compared with WT mice, tumor growth and tumor-associated angiogenesis was reduced in AT1aÀ/À mice with reduced expression of VEGFa. In AT1aÀ/À mice, administration of the AT1 receptor antagonist, TCV-116, showed further reductions of tumor growth, tumor-associated angiogenesis, and VEGFa expression. In vitro study, the expression of VEGFa mRNA and the production of VEGFa protein in LLC cells were significantly increased by AII, which were cancelled by AT1 receptor antagonist, CV-11974. Although the expression of other angiogenic factors, such as angiopoietin-1, angiopoietin-2, epidermal growth factor, and VEGF receptor 2 mRNA, was also investigated in tumor tissues, the expression of VEGFa was most correlated with tumor size among those other angiogenic factors. VEGFa induction by AT1 receptor-signaling in both host and tumor tissues is one of key regulators of tumor growth and tumor-associated angiogenesis. In conclusion, tumor tissue RAS as well as host tissue RAS were found to have an important role in tumor growth. AT1 receptor-signaling blockade may be a novel and effective target in the treatment of cancer. The renin-angiotensin system (RAS) plays important roles in the regulation of cardiovascular homeostasis and blood pressure. 1 Many pathophysiological activities of angiotensin II (AII) are known to be mediated by the seven transmembrane receptors. Two major subtypes of AII receptors, namely AT1 receptor and AT2 receptor, have been identified, with the former having receptor subtypes, AT1a and AT1b. 2 Most of AII functions in the cardiovascular system are mediated through the AT1 receptor, and in rodents they are mediated through the AT1a receptor. [3][4][5][6] Recently, many reports have suggested that AII is involved in other functions, such as apoptosis, vascular remodeling, and inflammation. 7-9 As regards vascular remodeling, several studies have shown that AII promotes proliferation, migration, and growth factor synthesis in several types of vascular cells, including smooth muscle cells and pericytes. [10][11][12][13] Other studies have also investigated the angiogenic effects of exogenous AII in vivo angiogenesis models. 14-17 Furthermore, recent studies have revealed local expression of several components of the RAS in various cancer cells and tissues. 18 A large-scale clinica...

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Heparin recovers AT1 receptor and its intracellular signal transduction in cultured vascular smooth muscle cells

Cited by 15 publications

References 19 publications

IP3 receptors regulate vascular smooth muscle contractility and hypertension

IP3 receptors regulate vascular smooth muscle contractility and hypertension

Expression of MAK-V/Hunk in renal distal tubules and its possible involvement in proliferative suppression

Roles for host and tumor angiotensin II type 1 receptor in tumor growth and tumor-associated angiogenesis

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