Angiotensin-converting enzyme inhibition modulates mitogen-activated protein kinase family expressions in the neonatal rat kidney

Byung Min Choi, Kee Hwan Yoo, Sun Bae In, Mee Hye Oh, Young Sook Hong, Won Lee Joo, Kyum Kim Soon

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Among the mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK) promotes cell proliferation or differentiation, whereas c-jun N terminal kinase (JNK) and p38 MAPK are thought to inhibit cell growth and induce apoptosis. The MAPK family may plays some role during kidney development, when large-scale proliferation and apoptosis have been observed to occur. Also, in this period, the renin-angiotensin system is markedly activated. We have demonstrated that angiotensin-converting enzyme inhibition in the developing rat kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. The aim of this study, therefore, was to examine the relationship between the MAPK family and renin-angiotensin system during neonatal renal development. Newborn rat pups were treated with enalapril (30 mg·kg-1·d-1) or normal saline for 7 d. Right kidneys of both groups were selected for immunohistochemical stains of MAPKs and activating transcription factor-2 (ATF-2), and left kidneys were selected for reverse transcriptase-PCR and immunoblot analysis of MAPKs, phospho-MAPKs, and ATF-2. To determine whether apoptosis is involved in the same tubules that highly expressed JNK and p38, we performed terminal deoxynucleotide transferase-mediated nick-end labeling stain for apoptotic cells and immunohistochemical stains for JNK-2, p38, and ATF-2 expression in the serial sections from the same kidney of the enalapril-treated group. In the enalapril-treated group, JNK-2, p38, phospho-JNK-2, phospho-p38, and ATF-2 protein expressions were significantly increased, and their immunoactivities were strongly detected in the proximal tubular epithelial cells in the cortex, compared with the control group. Especially JNK-2 and p38 expressions were highly activated and were spatially in accordance with the occurrence of apoptosis. ERK1/2 and phospho-ERK expressions were not changed by enalapril. These results suggest that the expressions of the MAPK family are modulated by angiotensin-converting enzyme inhibition in the developing kidney. JNK and p38 may be implicated to participate in angiotensin II-related intracellular signaling pathways of renal apoptosis in the developing kidney.

Original languageEnglish
Pages (from-to)115-123
Number of pages9
JournalPediatric Research
Volume57
Issue number1
DOIs
Publication statusPublished - 2005 Jan 1

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Peptidyl-Dipeptidase A
Mitogen-Activated Protein Kinases
Kidney
Activating Transcription Factor 2
Enalapril
Phosphotransferases
Apoptosis
Coloring Agents
Renin-Angiotensin System
Cell Proliferation
Inhibition (Psychology)
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
Growth
Transferases
Reverse Transcriptase Polymerase Chain Reaction
Angiotensin II
Cell Differentiation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Angiotensin-converting enzyme inhibition modulates mitogen-activated protein kinase family expressions in the neonatal rat kidney. / Choi, Byung Min; Yoo, Kee Hwan; In, Sun Bae; Oh, Mee Hye; Hong, Young Sook; Joo, Won Lee; Soon, Kyum Kim.

In: Pediatric Research, Vol. 57, No. 1, 01.01.2005, p. 115-123.

Research output: Contribution to journalArticle

Choi, Byung Min ; Yoo, Kee Hwan ; In, Sun Bae ; Oh, Mee Hye ; Hong, Young Sook ; Joo, Won Lee ; Soon, Kyum Kim. / Angiotensin-converting enzyme inhibition modulates mitogen-activated protein kinase family expressions in the neonatal rat kidney. In: Pediatric Research. 2005 ; Vol. 57, No. 1. pp. 115-123.
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