Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism.

Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism. Research Abstract Details 

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Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism. Abstract Text:

Shigehiko Eto,Masato Isome,Hideki Sano,Yutaka Fukuda,Yukihiko Kawasaki,Junzo Suzuki,Kazuei Igarashi,Joseph Satriano,Hitoshi Suzuki,

Polyamines play an essential role in the growth and differentiation of mammalian cells. The depletion of intracellular polyamines results in the suppression of growth. Proliferation of glomerular mesangial cells (MC) is the most common pathologic change in many forms of glomerulonephritis. Agmatine is a metabolite of arginine via arginine decarboxylase (ADC), highly expressed in the kidney, and unique in its capacity to suppress intracellular polyamine levels required for proliferation. As agmatine enters mammalian cells via the polyamine transport system, its antiproliferative effects may preferentially target cells with increased proliferative kinetics. In the present study, we evaluated the antiproliferative effects of agmatine on human MC in vitro. MC proliferation was stimulated with 20% fetal bovine serum (FBS) or platelet-derived growth factor (PDGF-BB, 20 ng/ml). Cell proliferation was measured using the (4.3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT) proliferation assay. Intracellular polyamine levels were assayed by high performance liquid chromatography, and cell death was assessed by cellular DNA fragmentation enzyme-linked immunosorbent assay. The MTT proliferation assay showed that agmatine significantly suppressed proliferation of human MC treated with 20% FBS or 5% FBS + PDGF as compared to human MC treated with 5% FBS. Polyamine levels were markedly lower in cells treated with agmatine, and proliferation was rescued by administration of putrescine. The fragmented DNA was hardly detected in agmatine-treated human MC. In summary, human MC stimulated to increase their proliferative kinetics are significantly more sensitive to the antiproliferative effects of agmatine than normally cultured cells. Suppressed proliferation of the agmatine-treated human MC is not due to increased cell death. These results suggest that agmatine is a promising drug candidate for the treatment of human mesangial proliferative glomerulonephritis.

Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism. Publishing Authors By Initials

S Eto,M Isome,H Sano,Y Fukuda,Y Kawasaki,J Suzuki,K Igarashi,J Satriano,H Suzuki,

For similar organic chemicals: amines: polyamines research abstracts see: organic chemicals: amines: polyamines research

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MEDLINE DATE:

Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Tohoku journal of experimental medicine

VOLUME: 210

Page Numbers: 145-51

Journal Abbreviation: Tohoku J. Exp. Med.

ISSN: 0040-8727

DAY: 3

MONTH: Oct

YEAR: 2006

Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 417355

Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism. Keywords Mesh Terms:

KEYWORDS: Polyamines

MESH TERMS: metabolism

Chemical & Substance for Abstract: Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism. Information

Substance Name: Agmatine

Registry Number: 306-60-5

Grant and Affiliation Information for Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism.

AFFILIATION: Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan.

Country: Japan

AGENCY: United States NIDDK

GRANT: DK070667

ACRONYM: DK

MEDLINETA: Tohoku J Exp Med

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