Mitochondrial dysfunction enhances the migration of vascular smooth muscles cells via suppression of Akt phosphorylation

Sun Young Ahn, Yon Sik Choi, Hyun Jung Koo, Jae Hoon Jeong, Wook Ha Park, Minseok Kim, Ying Piao, Youngmi Kim Pak

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Atherosclerosis is one of the major complications of diabetes, which may result from insulin resistance via mitochondrial dysfunction. Although a strong association between insulin resistance and cardiovascular disease has been suggested, it is not clear yet whether stress-inducing factors damage mitochondria and insulin signaling pathway in cardiovascular tissues. Methods: We investigated whether stress-induced mitochondrial dysfunction might alter the insulin/Akt signaling pathway in A10 rat vascular smooth muscle cells (VSMC). Results: The treatment of oxidized low density lipoprotein (oxLDL) decreased ATP contents, mitochondrial respiration activity, mRNA expressions of OXPHOS subunits and IRS-1/2 and insulin-mediated phosphorylations of Akt and AMP-activated protein kinase (AMPK). Similarly, dideoxycytidine (ddC), the mtDNA replication inhibitor, or rotenone, OXPHOS complex I inhibitor, inhibited the insulin-mediated pAkt while increased pAMPK regardless of insulin. Reciprocally, an inhibitor of Akt, triciribine (TCN), decreased cellular ATP contents. Overexpression of Akt dominant positive reversed the oxLDL- or ddC-mediated ATP decrease but AMPK activator did not. Akt activation also normalized the aberrant VSMC migration induced by ddC. Conclusions: Defective insulin signaling and mitochondrial function may collectively contribute to developing cardiovascular disease. General significance: Akt may be a possible therapeutic target for treating insulin resistance-associated atherosclerosis.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalBiochimica et Biophysica Acta - General Subjects
Volume1800
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

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Phosphorylation
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Cells
Zalcitabine
Insulin
Insulin Resistance
AMP-Activated Protein Kinases
Adenosine Triphosphate
triciribine
Atherosclerosis
Cardiovascular Diseases
Rotenone
antineoplaston A10
Diabetes Complications
Mitochondrial DNA
Cell Movement
Mitochondria
Respiration

Keywords

  • Akt/PKB
  • Atherosclerosis
  • Insulin signaling
  • Mitochondrial dysfunction
  • oxLDL
  • VSMC

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Mitochondrial dysfunction enhances the migration of vascular smooth muscles cells via suppression of Akt phosphorylation. / Ahn, Sun Young; Choi, Yon Sik; Koo, Hyun Jung; Jeong, Jae Hoon; Park, Wook Ha; Kim, Minseok; Piao, Ying; Pak, Youngmi Kim.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1800, No. 3, 01.03.2010, p. 275-281.

Research output: Contribution to journalArticle

Ahn, Sun Young ; Choi, Yon Sik ; Koo, Hyun Jung ; Jeong, Jae Hoon ; Park, Wook Ha ; Kim, Minseok ; Piao, Ying ; Pak, Youngmi Kim. / Mitochondrial dysfunction enhances the migration of vascular smooth muscles cells via suppression of Akt phosphorylation. In: Biochimica et Biophysica Acta - General Subjects. 2010 ; Vol. 1800, No. 3. pp. 275-281.
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