ADP-ribosyl cyclase in rat vascular smooth muscle cells properties and regulation

F. G S De Toledo, Jingfei Cheng, Mingyu Liang, Eduardo Nunes Chini, Thomas P. Dousa

Research output: Contribution to journalArticle

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Abstract

We investigated whether ADP-ribosyl cyclase (ADPR-cyclase) in rat vascular smooth muscle cells (VSMCs) has enzymatic properties that differ from the well-characterized CD38-antigen ADPR-cyclase, expressed in HL-60 cells. ADPR-cyclase from VSMCs, but not CD38 ADPR-cyclase from HL-60 cells, was inhibited by gangliosides (10 μmol/L) GT1(B), GD1 and GM3. Preincubation of membranes from CD38 HL-60 cells, but not from VSMCs, with anti-CD38 antibodies increased ADPR-cyclase activity; CD38 antigen was detected both in VSMCs and in HL-60 cells. ADPR-cyclase in VSMC membranes was more sensitive than CD38 HL-60 ADPR-cyclase to inactivation by N- endoglycosidase F and to thermal inactivation at 45°C. The specific activity of ADPR-cyclase in membranes from VSMCs was >20-fold higher than in membranes from CD38 HL-60 cells. Most importantly, VSMC ADPR-cyclase was inhibited by Zn2+ and Cu2+ ions; the inhibition by Zn2+ was dose dependent, noncompetitive, and reversible by EDTA. In contrast, Zn2+ stimulated the activity of CD38 HL-60 ADPR-cyclase and other known types of ADPR-cyclases. Retinoids act either via the nuclear receptor retinoic acid receptor or retinoid X receptor, including all-trans retinoic acid (atRA), and panagonist 9-cis-retinoic acid - upregulated VSMC ADPR-cyclase; the stimulatory effect of atRA was blocked by actinomycin D and cycloheximide. 1,25(OH)2-Vitamin D3 (calciferol) stimulated VSMC ADPR-cyclase dose dependently at subnanomolar concentrations (ED50≃56 pmol/L). Oral administration of atRA to rats resulted in an increase of ADPR-cyclase activity in aorta (≃ + 60%) and, to a lesser degree, in myocardium of left ventricle (+ 18%), but atRA had no effect on ADPR-cyclases in lungs, spleen, intestinal smooth muscle, skeletal muscle, liver, or testis. Administration of 3,5,3'-triiodothyronine (T3) to rats resulted in an increase of ADPR-cyclase activity in aorta (≃ + 89%), but not in liver or brain. We conclude the following: (1) ADPR-cyclase in VSMCs has enzymatic properties distinct from 'classic' CD38 ADPR-cyclase, especially sensitivity to inhibition by Zn2+ and Cu2+; (2) ADPR-cyclase in VSMCs is upregulated by various retinoids, calcitriol, and T3 in vitro; and (3) administration of atRA and T3 increases ADPR-cyclase in aorta in vivo. We suggest that the cADPR signaling system plays an important role in the regulation of VSMC functions in response to steroid superfamily hormones.

Original languageEnglish (US)
Pages (from-to)1153-1159
Number of pages7
JournalCirculation Research
Volume86
Issue number11
StatePublished - Jun 9 2000

Fingerprint

ADP-ribosyl Cyclase
Vascular Smooth Muscle
Smooth Muscle Myocytes
HL-60 Cells
Tretinoin
CD38 Antigens
Aorta
Retinoids
Membranes

Keywords

  • ADP-ribose
  • Antibodies
  • Calciferols
  • Retinoids
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

De Toledo, F. G. S., Cheng, J., Liang, M., Chini, E. N., & Dousa, T. P. (2000). ADP-ribosyl cyclase in rat vascular smooth muscle cells properties and regulation. Circulation Research, 86(11), 1153-1159.

ADP-ribosyl cyclase in rat vascular smooth muscle cells properties and regulation. / De Toledo, F. G S; Cheng, Jingfei; Liang, Mingyu; Chini, Eduardo Nunes; Dousa, Thomas P.

In: Circulation Research, Vol. 86, No. 11, 09.06.2000, p. 1153-1159.

Research output: Contribution to journalArticle

De Toledo, FGS, Cheng, J, Liang, M, Chini, EN & Dousa, TP 2000, 'ADP-ribosyl cyclase in rat vascular smooth muscle cells properties and regulation', Circulation Research, vol. 86, no. 11, pp. 1153-1159.
De Toledo FGS, Cheng J, Liang M, Chini EN, Dousa TP. ADP-ribosyl cyclase in rat vascular smooth muscle cells properties and regulation. Circulation Research. 2000 Jun 9;86(11):1153-1159.
De Toledo, F. G S ; Cheng, Jingfei ; Liang, Mingyu ; Chini, Eduardo Nunes ; Dousa, Thomas P. / ADP-ribosyl cyclase in rat vascular smooth muscle cells properties and regulation. In: Circulation Research. 2000 ; Vol. 86, No. 11. pp. 1153-1159.
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TY - JOUR

T1 - ADP-ribosyl cyclase in rat vascular smooth muscle cells properties and regulation

AU - De Toledo, F. G S

AU - Cheng, Jingfei

AU - Liang, Mingyu

AU - Chini, Eduardo Nunes

AU - Dousa, Thomas P.

PY - 2000/6/9

Y1 - 2000/6/9

N2 - We investigated whether ADP-ribosyl cyclase (ADPR-cyclase) in rat vascular smooth muscle cells (VSMCs) has enzymatic properties that differ from the well-characterized CD38-antigen ADPR-cyclase, expressed in HL-60 cells. ADPR-cyclase from VSMCs, but not CD38 ADPR-cyclase from HL-60 cells, was inhibited by gangliosides (10 μmol/L) GT1(B), GD1 and GM3. Preincubation of membranes from CD38 HL-60 cells, but not from VSMCs, with anti-CD38 antibodies increased ADPR-cyclase activity; CD38 antigen was detected both in VSMCs and in HL-60 cells. ADPR-cyclase in VSMC membranes was more sensitive than CD38 HL-60 ADPR-cyclase to inactivation by N- endoglycosidase F and to thermal inactivation at 45°C. The specific activity of ADPR-cyclase in membranes from VSMCs was >20-fold higher than in membranes from CD38 HL-60 cells. Most importantly, VSMC ADPR-cyclase was inhibited by Zn2+ and Cu2+ ions; the inhibition by Zn2+ was dose dependent, noncompetitive, and reversible by EDTA. In contrast, Zn2+ stimulated the activity of CD38 HL-60 ADPR-cyclase and other known types of ADPR-cyclases. Retinoids act either via the nuclear receptor retinoic acid receptor or retinoid X receptor, including all-trans retinoic acid (atRA), and panagonist 9-cis-retinoic acid - upregulated VSMC ADPR-cyclase; the stimulatory effect of atRA was blocked by actinomycin D and cycloheximide. 1,25(OH)2-Vitamin D3 (calciferol) stimulated VSMC ADPR-cyclase dose dependently at subnanomolar concentrations (ED50≃56 pmol/L). Oral administration of atRA to rats resulted in an increase of ADPR-cyclase activity in aorta (≃ + 60%) and, to a lesser degree, in myocardium of left ventricle (+ 18%), but atRA had no effect on ADPR-cyclases in lungs, spleen, intestinal smooth muscle, skeletal muscle, liver, or testis. Administration of 3,5,3'-triiodothyronine (T3) to rats resulted in an increase of ADPR-cyclase activity in aorta (≃ + 89%), but not in liver or brain. We conclude the following: (1) ADPR-cyclase in VSMCs has enzymatic properties distinct from 'classic' CD38 ADPR-cyclase, especially sensitivity to inhibition by Zn2+ and Cu2+; (2) ADPR-cyclase in VSMCs is upregulated by various retinoids, calcitriol, and T3 in vitro; and (3) administration of atRA and T3 increases ADPR-cyclase in aorta in vivo. We suggest that the cADPR signaling system plays an important role in the regulation of VSMC functions in response to steroid superfamily hormones.

AB - We investigated whether ADP-ribosyl cyclase (ADPR-cyclase) in rat vascular smooth muscle cells (VSMCs) has enzymatic properties that differ from the well-characterized CD38-antigen ADPR-cyclase, expressed in HL-60 cells. ADPR-cyclase from VSMCs, but not CD38 ADPR-cyclase from HL-60 cells, was inhibited by gangliosides (10 μmol/L) GT1(B), GD1 and GM3. Preincubation of membranes from CD38 HL-60 cells, but not from VSMCs, with anti-CD38 antibodies increased ADPR-cyclase activity; CD38 antigen was detected both in VSMCs and in HL-60 cells. ADPR-cyclase in VSMC membranes was more sensitive than CD38 HL-60 ADPR-cyclase to inactivation by N- endoglycosidase F and to thermal inactivation at 45°C. The specific activity of ADPR-cyclase in membranes from VSMCs was >20-fold higher than in membranes from CD38 HL-60 cells. Most importantly, VSMC ADPR-cyclase was inhibited by Zn2+ and Cu2+ ions; the inhibition by Zn2+ was dose dependent, noncompetitive, and reversible by EDTA. In contrast, Zn2+ stimulated the activity of CD38 HL-60 ADPR-cyclase and other known types of ADPR-cyclases. Retinoids act either via the nuclear receptor retinoic acid receptor or retinoid X receptor, including all-trans retinoic acid (atRA), and panagonist 9-cis-retinoic acid - upregulated VSMC ADPR-cyclase; the stimulatory effect of atRA was blocked by actinomycin D and cycloheximide. 1,25(OH)2-Vitamin D3 (calciferol) stimulated VSMC ADPR-cyclase dose dependently at subnanomolar concentrations (ED50≃56 pmol/L). Oral administration of atRA to rats resulted in an increase of ADPR-cyclase activity in aorta (≃ + 60%) and, to a lesser degree, in myocardium of left ventricle (+ 18%), but atRA had no effect on ADPR-cyclases in lungs, spleen, intestinal smooth muscle, skeletal muscle, liver, or testis. Administration of 3,5,3'-triiodothyronine (T3) to rats resulted in an increase of ADPR-cyclase activity in aorta (≃ + 89%), but not in liver or brain. We conclude the following: (1) ADPR-cyclase in VSMCs has enzymatic properties distinct from 'classic' CD38 ADPR-cyclase, especially sensitivity to inhibition by Zn2+ and Cu2+; (2) ADPR-cyclase in VSMCs is upregulated by various retinoids, calcitriol, and T3 in vitro; and (3) administration of atRA and T3 increases ADPR-cyclase in aorta in vivo. We suggest that the cADPR signaling system plays an important role in the regulation of VSMC functions in response to steroid superfamily hormones.

KW - ADP-ribose

KW - Antibodies

KW - Calciferols

KW - Retinoids

KW - Vascular smooth muscle cells

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