Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells.

Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells. Research Abstract Details 

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Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells. Abstract Text:

Zabeena P Shaik,E Kim Fifer,Grazyna Nowak,Zabeena P Shaik,E Kim Fifer,Grazyna Nowak,

Protein kinase B (Akt) activation is well known for its protective effects against apoptosis. However, the role of Akt in regulation of necrosis is unknown. This study was designed to test whether Akt activation protects against nephrotoxicant-induced injury and death in renal proximal tubular cells (RPTC). Exposure of primary cultures of RPTC to the nephrotoxic cysteine conjugate, S-(1,2-dichlorovinyl)-l-cysteine (DCVC), resulted in 9% apoptosis and 30% necrosis at 24 h following the exposure. Akt was activated during 8 h but not at 24 h following toxicant exposure. No RPTC necrosis was observed during Akt activation. Blocking Akt activation using a phosphatidylinositol 3-kinase inhibitor, LY294002 (20 muM), or expressing dominant negative (inactive) Akt increased DCVC-induced RPTC necrosis to 42%. In contrast, Akt activation by expression of constitutively active Akt diminished necrosis to 15%. Modulation of Akt activity had no effect on DCVC-induced apoptosis. DCVC-induced RPTC injury was accompanied by decreases in respiration (51% of controls) and ATP levels (57% of controls). Akt inhibition exacerbated decreases in RPTC respiration and intracellular ATP content (both to 30% of controls). In contrast, Akt activation reduced DCVC-induced decreases in respiration (80% of controls) and prevented decline in ATP content. These data show that in RPTC, Akt activation reduces 1) toxicant-induced mitochondrial dysfunction, 2) decreases in ATP levels, and 3) necrosis. We conclude that Akt activation plays a protective role against necrosis caused by nephrotoxic insult in RPTC. Furthermore, we identified mitochondria as a subcellular target of protective actions of Akt against necrosis.

Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells. Publishing Authors By Initials

ZP Shaik,EK Fifer,G Nowak,ZP Shaik,EK Fifer,G Nowak,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of physiology. Renal physiology

VOLUME: 292

Page Numbers: F292-303

Journal Abbreviation: Am. J. Physiol. Renal Physiol.

ISSN: 0363-6127

DAY: 29

MONTH: 08

YEAR: 2006

Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100901990

Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: physiology

Chemical & Substance for Abstract: Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells.

AFFILIATION: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R01-DK-59558

ACRONYM: DK

MEDLINETA: Am J Physiol Renal Physiol

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