Ahn 2010 Biochim Biophys Acta

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Ahn SY, Choi YS, Koo HJ, Jeong JH, Park WH, Kim M, Piao Y, Pak YK (2010) Mitochondrial dysfunction enhances the migration of vascular smooth muscles cells via suppression of Akt phosphorylation. Biochim Biophys Acta 1800:275-81.

» PMID: 19781600

Ahn SY, Choi YS, Koo HJ, Jeong JH, Park WH, Kim M, Piao Y, Pak YK (2010) Biochim Biophys Acta

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.

Keywords: VSMC, Insulin signaling, Mitochondrial dysfunction, Atherosclerosis, Akt/PKB, oxLDL

O2k-Network Lab: KR Seoul Pak YK


Labels: Pathology: Diabetes 

Organism: Rat  Tissue;cell: Skeletal muscle  Preparation: Intact cells 



HRR: Oxygraph-2k