The ASK1-MAP Kinase Cascades in Mammalian Stress Response

Matsukawa, Jun; Matsuzawa, Atsushi; Takeda, Kohsuke; Ichijo, Hidenori

doi:10.1093/jb/mvh134

Cited by 312 publications

(289 citation statements)

References 42 publications

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“…ASK1 is known to be one of the key molecules that is involved in oxidative stress-induced cellular apoptosis. 14,21 These findings encouraged us to determine the role of ASK1 and VEGF in oxidative stress-induced endothelial apoptosis. Using cultured endothelial cells from wild-type and ASK1-deficient mice, we found that ASK1 deficiencies significantly attenuated H 2 O 2 -induced endothelial apoptosis, demonstrating the important role of ASK1 in oxidative stress-induced endothelial apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF

et al. 2011

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This study was undertaken to elucidate a novel mechanism underlying angiotensin II-induced cardiac injury, focusing on the role of oxidative stress and myocardial capillary density. Salt-loaded Dahl salt-sensitive hypertensive rats (DS rats), a useful model for hypertensive cardiac remodeling or heart failure, were orally given irbesartan (an AT1 receptor blocker), tempol (a superoxide dismutase mimetic) or hydralazine (a vasodilator). Irbesartan significantly ameliorated left ventricular ischemia and prevented the development of cardiac hypertrophy and fibrosis in DS rats. The benefits were associated with the attenuation of oxidative stress, normalization of myocardial capillary density and inhibition of capillary endothelial apoptosis. Moreover, DS rats with significant cardiac hypertrophy and fibrosis displayed decreased myocardial vascular endothelial growth factor (VEGF) expression and increased cardiac apoptosis signal-regulating kinase 1 (ASK1) activation. Treatment with irbesartan significantly reversed these phenotypes. Tempol treatment of DS rats mimicked all the above-mentioned effects of irbesartan, indicating the critical role of oxidative stress in cardiac injury. We also investigated the role of VEGF and ASK1 in oxidative stress-induced endothelial apoptosis by using cultured endothelial cells from wild-type and ASK1-deficient mice. Oxidative stress-induced ASK1 activation led to endothelial apoptosis, and VEGF treatment prevented oxidative stress-induced endothelial apoptosis by inhibiting ASK1 activation. We obtained the first evidence that oxidative stress-induced cardiac VEGF repression and ASK1 activation caused the enhancement of endothelial apoptosis and contributed to a decrease in myocardial capillary density. These effects resulted in angiotensin II-induced progression of cardiac injury.

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Section: Discussionmentioning

confidence: 99%

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF

et al. 2011

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“…In mammalian cells, ASK1 participates in the JNK and p38 MAPK signaling cascades by phosphorylating MKK4/MKK7 and MKK3/MKK6 respectively . ASK1 is activated in response to various extracellular and intracellular stimuli, such as lipopolysaccharide, ROS, endoplasmic reticulum (ER) stress, and signaling through Fas and TNFa (Matsukawa et al 2004). ASK1 is well known as a proapoptotic, stress-activated signaling molecule, and it is under tight regulation at multiple levels, one of which is negatively regulated by PRDX1 (Kim et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Suppression of MG132-mediated cell death by peroxiredoxin 1 through influence on ASK1 activation in human thyroid cancer cells

Du¹,

Yan²,

Zhang³

et al. 2010

Endocrine-Related Cancer

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Proteasome inhibitors represent a novel class of antitumor agents with pre-clinical and clinical evidence of activity against hematologic malignancies and solid tumors. However, emerging evidence indicates that antiapoptotic factors may also accumulate as a consequence of exposure to these drugs, thus it seems plausible that the activation of survival signaling cascades might compromise their antitumoral effects. Peroxiredoxins (PRDXs) are a family of thiol-containing peroxidases identified primarily by their ability to remove cellular hydroperoxides. The function of PRDX1 in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Another important finding is that aberrant upregulation of PRDX1 has been discovered in various cancers. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase that is regulated under conditions of cellular stress. ASK1 phosphorylates c-Jun N-terminal kinase and p38 MAPK, and elicits an apoptotic response. ASK1 activity is regulated at multiple levels, one of which is through interaction with PRDX1. In this study, for the first time we report that upregulation of PRDX1 expression was found in thyroid cancer cells treated with proteasome inhibitors, and PRDX1 knockdown resulted in accelerated proteasome inhibitor-induced cell death. In addition, we demonstrated that ASK1 activity was implicated in the PRDX1-dependent response of thyroid cancer cells to proteasome inhibitormediated cell death.

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“…ASK1 was identified as a MAP kinase kinase kinase involved in the stress-induced apoptosis signaling cascade that activates the SEK1-Jun N-terminal kinase (JNK) and MKK-p38 MAP kinase cascade [16]. ASK1 is activated by death receptor ligands, such as TNF-a and Fas ligand, and by various cytotoxic stresses, such as hydrogen peroxide, anticancer drugs, and growth factor deprivation [17]. Furthermore, endoplasmic reticulum stress and G protein-coupled receptor signaling were recently shown to activate ASK1 [17].…”

Section: Introductionmentioning

confidence: 99%

New mechanisms of skin innate immunity: ASK1-mediated keratinocyte differentiation regulates the expression of β-defensins, LL37, and TLR2

et al. 2005

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Epidermal keratinocytes differentiate and form a multilayered epidermis, which is the primary barrier between the body and the outer environment. As the epidermis is constantly exposed to a variety of microbial pathogens, its function of resisting microbial pathogens is vital. This characteristic feature is formed during differentiation. Immunohistochemical analysis revealed that the upper epidermis of normal human skin expresses b-defensins 1-3 and LL37. We hypothesized that epidermal keratinocytes develop an innate immune barrier based on human b-defensins (hBD) and LL37 during differentiation. To prove this, we introduced an active form of the apoptosis signalregulating kinase-1 (ASK1), an intracellular regulator of keratinocyte differentiation, into cultured normal human keratinocytes. Transfection of this active form, ASK1-DN, significantly enhanced the expression of hBD1-3 and LL37. In addition, a p38 inhibitor abolished this induction, indicating that the ASK1-p38 cascade regulates the expression of hBD1-3 and LL37. Furthermore, the ASK1-p38 pathway also regulated the expression of Toll-like receptor (TLR)2 in keratinocytes. Contact between S. aureus and keratinocytes resulted in the phosphorylation of p38 and induced the expression of hBD2 and hBD3. Moreover, the p38 inhibitor reduced this induction. In conclusion, the ASK1-p38 cascade regulates the innate immunity of the skin by forming an immune barrier consisting of hBD, LL37, and TLR2 during epidermal differentiation.

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The ASK1-MAP Kinase Cascades in Mammalian Stress Response

Cited by 312 publications

References 42 publications

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF

Suppression of MG132-mediated cell death by peroxiredoxin 1 through influence on ASK1 activation in human thyroid cancer cells

New mechanisms of skin innate immunity: ASK1-mediated keratinocyte differentiation regulates the expression of β-defensins, LL37, and TLR2

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