Activation of the Ste20-like Oxidant Stress Response Kinase-1 during the Initial Stages of Chemical Anoxia-induced Necrotic Cell Death

Pombo, Celia M.; Tsujita, Toshiya; Kyriakis, John; Bonventre, Joseph V.; Force, Thomas

doi:10.1074/jbc.272.46.29372

Cited by 41 publications

(45 citation statements)

References 57 publications

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“…Previously, incubation with H 2 O 2 has been shown to activate STK25 after immunoprecipitation from Ramos B cells or Madin-Darby canine kidney epithelial cells [9]. Interestingly, in this study the treatment of L6 myoblasts with the proinflammatory myokine, TNF-α, as well as menadione and H 2 O 2 , both causing oxidative stress, was shown to regulate the activity of STK25 at the level of phosphorylation.…”

Section: Discussionmentioning

confidence: 75%

“…In these conditions, downregulation of STK25 by RNA interference enhanced cell survival while overexpression of STK25 elicited apoptotic cell death [8]. The only known substrates for STK25 are myelin basic protein (MBP) [9], Golgi-associated 14-3-3ζ [5] and CCM3 [7]. To our knowledge, there are no studies suggesting a possible function for STK25 in metabolic regulation.…”

Section: Introductionmentioning

confidence: 85%

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Serine/threonine protein kinase 25 (STK25): a novel negative regulator of lipid and glucose metabolism in rodent and human skeletal muscle

et al. 2012

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Aims/hypothesis This study investigates the role of serine/ threonine protein kinase 25 (STK25), a member of the sterile 20 (STE20) superfamily of kinases, in the regulation of skeletal muscle metabolism. Methods The effect of depleting STK25 in muscle cells was studied by reducing the mRNA and protein content of this target in the rat myoblast cell line L6 by small interfering (si)RNA. The changes in the mRNA and protein levels of several members of the fatty acid oxidative and glucose metabolic pathways were measured by quantitative realtime (qRT)-PCR and western blot. The rate of palmitate oxidation and glucose uptake was measured after transfection with siRNA for Stk25. Expression of STK25 was also evaluated in skeletal muscle biopsies from 41 white Europid men and women with normal and impaired glucose tolerance and type 2 diabetes using qRT-PCR. Results We demonstrate that partial depletion of STK25 increases the expression of uncoupling protein 3 (Ucp3), accompanied by increased lipid oxidation, in myoblasts. In addition, a reduced level of STK25 enhances the expression of Slc2a1 (also known as Glut1), Slc2a4 (also known as Glut4) and hexokinase 2, and correspondingly, improves insulin-stimulated glucose uptake in muscle cells. Consistent with these results, significantly higher STK25 levels were observed in the skeletal muscle of type 2 diabetic patients, compared with individuals with normal glucose tolerance. Conclusions/interpretation This is the first study indicating a possible role for STK25 in the regulation of glucose and lipid metabolism in L6 myoblasts. This kinase appears to be an interesting new mediator to be evaluated for therapeutic intervention in type 2 diabetes and related complications, as controlled increase in lipid oxidation and insulin-stimulated glucose uptake in skeletal muscle is favourable and can restore energy balance in metabolically compromised states.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 85%

Serine/threonine protein kinase 25 (STK25): a novel negative regulator of lipid and glucose metabolism in rodent and human skeletal muscle

et al. 2012

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“…Ste20-homologous proteins (e.g., STK25) are implicated as important transducers of signals from the p21 family of GTPases (55,56), can be activated by cellular stress, and are important mediators of oxidant-mediated signal transduction (57,58). In this study arsenite robustly induced NHEK stk25 expression, an effect more profound in primary cells, and an effect attenuated by reducing GSH level with BSO.…”

Section: Discussionmentioning

confidence: 74%

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Trouba

Geisenhoffer

Germolec

2002

Environ Health Perspect

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Arsenic is a carcinogen that poses a significant health risk in humans. Based on evidence that arsenic has differential effects on human, rodent, normal, and transformed cells, these studies addressed the relative merits of using normal human epidermal keratinocytes (NHEK) and immortalized human (HaCaT) and mouse (HEL30) keratinocytes when examining stressinduced gene expression that may contribute to carcinogenesis. We hypothesize that redox-related gene expression is differentially modulated by arsenic in normal versus immortalized keratinocytes. To test the hypothesis, we exposed keratinocytes to sodium arsenite for 4 or 24 hr, at which time serine threonine kinase-25 (

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“…With sufficient oxygenation and energy supply, the interior cells were capable of maintaining their volume by pumping ions, especially Na + , out of the cell. In our experiments, when ATP production was inhibited by CN, an electron transport chain decoupler (Pombo et al 1997), and 2DG, an inhibitor of anaerobic respiration, the tissue swelled because pumping slowed or ceased. When membrane integrity was disrupted with Triton X-100, the tissue swelled because ionic pumps were not capable of counteracting the rapid influx of ions.…”

Section: Discussionmentioning

confidence: 99%

Fixed negative charge and the Donnan effect: a description of the driving forces associated with brain tissue swelling and oedema

Elkin

Shaik

Morrison

2010

Phil. Trans. R. Soc. A.

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Cerebral oedema or brain tissue swelling is a significant complication following traumatic brain injury or stroke that can increase the intracranial pressure (ICP) and impair blood flow. Here, we have identified a potential driver of oedema: the negatively charged molecules fixed within cells. This fixed charge density (FCD), once exposed, could increase ICP through the Donnan effect. We have shown that metabolic processes and membrane integrity are required for concealing this FCD as slices of rat cortex swelled immediately (within 30 min) following dissection if treated with 2 deoxyglucose + cyanide (2DG+CN) or Triton X-100. Slices given ample oxygen and glucose, however, did not swell significantly. We also found that dead brain tissue swells and shrinks in response to changes in ionic strength of the bathing medium, which suggests that the Donnan effect is capable of pressurizing and swelling brain tissue. As predicted, a non-ionic osmolyte, 1,2 propanediol, elicited no volume change at 2000 × 10 −3 osmoles l −1 (Osm). Swelling data were well described by triphasic mixture theory with the calculated reference state FCD similar to that measured with a 1,9 dimethylmethylene blue assay. Taken together, these data suggest that intracellular fixed charges may contribute to the driving forces responsible for brain swelling.

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Activation of the Ste20-like Oxidant Stress Response Kinase-1 during the Initial Stages of Chemical Anoxia-induced Necrotic Cell Death

Cited by 41 publications

References 57 publications

Serine/threonine protein kinase 25 (STK25): a novel negative regulator of lipid and glucose metabolism in rodent and human skeletal muscle

Serine/threonine protein kinase 25 (STK25): a novel negative regulator of lipid and glucose metabolism in rodent and human skeletal muscle

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Fixed negative charge and the Donnan effect: a description of the driving forces associated with brain tissue swelling and oedema

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