Effect of probucol on intracellular pH and proliferation of human vascular endothelial cells

Komatsu, Sumio; Sawada, Shohei; Tamagaki, Toshiyuki; Tsuda, Yoshiyuki; Kono, Yoshihito; Higaki, Tadashi; Imamura, Hitoshi; Tada, Yuusuke; Yamasaki, Seiki; Toratani, Akihisa; Sato, Toshiyuki; Akamatsu, Naoaki; Tsuji, Hajime; Nakagawa, Masao

doi:10.1016/s1056-8719(99)00019-2

Cited by 8 publications

(5 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell proliferation is also dependent on modulation of [Ca 2ϩ ] i (43). Our data suggest that K5 interferes with both cytosolic pH i and [Ca 2ϩ ] i in HUVEC.…”

Section: Analyses Of Sequence Similarities Between Sk and Humanmentioning

confidence: 65%

See 1 more Smart Citation

The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

Gonzalez-Gronow

Kalfa

Johnson

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Human plasminogen contains structural domains that are termed kringles. Proteolytic cleavage of plasminogen yields kringles 1-3 or 4 and kringle 5 (K5), which regulate endothelial cell proliferation. The receptor for kringles 1-3 or 4 has been identified as cell surfaceassociated ATP synthase; however, the receptor for K5 is not known. Sequence homology exists between the plasminogen activator streptokinase and the human voltagedependent anion channel (VDAC); however, a functional relationship between these proteins has not been reported. A streptokinase binding site for K5 is located between residues Tyr 252 -Lys 283 , which is homologous to the primary sequence of VDAC residues Tyr 224 -Lys 255 . Antibodies against these sequences react with VDAC and detect this protein on the plasma membrane of human endothelial cells. K5 binds with high affinity (K d of 28 nM) to endothelial cells, and binding is inhibited by these antibodies. Purified VDAC binds to K5 but only when reconstituted into liposomes. K5 also interferes with mechanisms controlling the regulation of intracellular Ca 2؉ via its interaction with VDAC. K5 binding to endothelial cells also induces a decrease in intracellular pH and hyperpolarization of the mitochondrial membrane. These studies suggest that VDAC is a receptor for K5.

show abstract

“…Cell proliferation is also dependent on modulation of [Ca 2ϩ ] i (43). Our data suggest that K5 interferes with both cytosolic pH i and [Ca 2ϩ ] i in HUVEC.…”

Section: Analyses Of Sequence Similarities Between Sk and Humanmentioning

confidence: 65%

“…Endothelial cell proliferation is preceded by an increase in cytosolic pH i , leading to angiogenesis and the repair of injured endothelial cells (43). Cell proliferation is also dependent on modulation of [Ca 2ϩ ] i (43).…”

Section: Analyses Of Sequence Similarities Between Sk and Humanmentioning

confidence: 99%

The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

Gonzalez-Gronow

Kalfa

Johnson

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Interaction of K5 with its receptor, the voltagedependent anion channel (VDAC1), interferes with both cytosolic intracellular free Ca 2þ signaling and pH regulation in HUVEC [Gonzalez-Gronow et al, 2003]. Angiogenesis and repair of blood vessels was preceded by increases in cytosolic pH in EC [Komatsu et al, 1999]. Interference of these mechanisms by K5 may be the basis of its anti-angiogenic activity.…”

Section: Kringle 5 Also Has Anti-angiogenic Activitymentioning

confidence: 99%

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

114

View full text Add to dashboard Cite

Tumor growth requires the development of new vessels that sprout from pre-existing normal vessels in a process known as ''angiogenesis'' [Folkman (1971) N Engl J Med 285:1182-1186. These new vessels arise from local capillaries, arteries, and veins in response to the release of soluble growth factors from the tumor mass, enabling these tumors to grow beyond the diffusion-limited size of approximately 2 mm diameter. Angiostatin, a naturally occurring inhibitor of angiogenesis, was discovered based on its ability to block tumor growth in vivo by inhibiting the formation of new tumor blood vessels [O'Reilly et al. (1994a) Cold Spring Harb Symp Quant Biol 59:471-482]. Angiostatin is a proteolytically derived internal fragment of plasminogen and may contain various members of the five plasminogen ''kringle'' domains, depending on the exact sites of proteolysis. Different forms of angiostatin have measurably different activities, suggesting that much remains to be elucidated about angiostatin biology. A number of groups have sought to identify the native cell surface binding site(s) for angiostatin, resulting in at least five different binding sites proposed for angiostatin on the surface of endothelial cells (EC). This review will consider the data supporting all of the various reported angiostatin binding sites and will focus particular attention on the angiostatin binding protein identified by our group: F 1 F O ATP synthase. There have been several developments in the quest to elucidate the mechanism of action of angiostatin and the regulation of its receptor. The purpose of this review is to describe the highlights of research on the mechanism of action of angiostatin, its' interaction with ATP synthase on the EC surface, modulators of its activity, and issues that should be explored in future research related to angiostatin and other anti-angiogenic agents.

show abstract

“…It has been reported that probucol could preserve endothelial function by enhancing prostacyclin generation [42], reducing the level of endogenous nitric oxide (NO) synthase inhibitor [43], and inhibiting the expression of various adhesion molecules [44]. Probucol could also promote proliferation [42] and reduce apoptosis of endothelial cells that induced by oxidative injury [45][46][47].…”

Section: Introductionmentioning

confidence: 99%

Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo

Zhang

Chen

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Oxidized low-density lipoprotein (ox-LDL) is a major component of hyperlipidemia and contributes to atherosclerosis. Endothelial progenitor cells (EPCs) play an important role in preventing atherosclerosis and notably decreased in hyperlipidemia. Ox-LDL and ox-LDL-related reactive oxygen species (ROS) have deleterious effects on EPCs. Probucol as an antioxidant and anti-inflammatory drug reduces ROS production. The present study was to determine if probucol could protect EPCs from ox-LDL in vivo and to investigate the potential mechanisms. Methods: ox-LDL was injected into male C57BL/6 mice for 3 days with or without probucol treatment with PBS as control. Bone marrow (BM) fluid, serum, circulating mononuclear cells (MNCs) and EPCs were collected for analysis. Results: the increased extracellular ROS in BM, serum and blood intracellular ROS production in the mice with ox-LDL treatment in association with a significant reduction of circulating MNCs and EPCs were restored with Probucol treatment. A significant increase in the serum ox-LDL and C-reactive protein and decrease in superoxide dismutase and circulating MNCs and EPCs were observed in hyperlipidemic patients that were effectively reversed with probucol treatment. Conclusion: these data suggested that probucol could protect EPCs from ox-LDL through inhibition of ROS production in vivo.

show abstract

Effect of probucol on intracellular pH and proliferation of human vascular endothelial cells

Cited by 8 publications

References 32 publications

The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo

Contact Info

Product

Resources

About