Background Estrogen deficiency results in loss of bone mass compounds with estrogen-like activity that bind to estrogen receptors effect of the phytoestrogen puerarin on adult mouse osteoblasts. Methods Osteoblast cel...Background Estrogen deficiency results in loss of bone mass compounds with estrogen-like activity that bind to estrogen receptors effect of the phytoestrogen puerarin on adult mouse osteoblasts. Methods Osteoblast cells were harvested from 8-month old female Phytoestrogens are plant-derived non-steroidal The main aim of this study was to investigate the mprinting control region （ICR） mice. The effects of puerarin stimulation on the proliferation, differentiation and maturation of osteoblasts were examined. The production of nitric oxide （NO） and the expression of bone morphogenetic protein-2 （BMP-2）, SMAD4, mitogen-activated protein kinases （MAPK）, core binding factor all runt-related transcription factor 2 （Cbfal/Runx2）, osteoprotegerin （OPG）, and receptor activator of NF-KB ligand （RANKL） genes were analyzed. The activation of signal pathways was further confirmed by specific pathway inhibitors. Results The osteoblast viability reached its maximum at 10-8 mol/L puerarin. At this concentration, puerarin increases the proliferation and matrix mineralization of osteoblasts and promotes NO synthesis. With 108 mol/L puerarin treatment, BMP-2, SMAD4, Cbfal/Runx2, and OPG gene expression were up-regulated, while the RANKL gene expression is down-regulated. Concurrent treatment involving the （bone morphogenetic protein） BMP antagonist Noggin or the NOS inhibitor L-NAME diminishes puerarin induced cell proliferation, Alkaline phosphatase （ALP） activity, NO production, as well as the BMP-2, SMAD4, Cbfal/Runx2, OPG, and RANKL gene expression. Conclusions In this in vitro study, we demonstrate that puerarin is a bone anabolic agent that exerts its osteogenic effects through the induction of BMP-2 and NO synthesis, subsequently regulating Cbfal/Runx2, OPG, and RANKL gene expression. This effect may contribute to its induction of osteoblast proliferation and differentiation, resulting in bone formation.展开更多
Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the ...Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.展开更多
Bone morphogenetic proteins （BMPs） induce ectopic bone formation and promote osteoblast differentiation. It has been documented that Smad transcriptional factors function as primary mediators of BMPs activity. Recep...Bone morphogenetic proteins （BMPs） induce ectopic bone formation and promote osteoblast differentiation. It has been documented that Smad transcriptional factors function as primary mediators of BMPs activity. Receptor-regulated Smad （Smad1, 5, 8） could be phosphorylated by activated BMPR-I and form complex with Smad4. The Smad complex translocates to the nucleus and regulate target gene transcription. Recently, several reports suggested that Mitogen-Activated Protein Kinase （MAPK） signaling pathways could be initiated downstream of the BMP receptor complex. Alkaline phosphatase （ALP） is an early marker of osteoblast differentiation Both ALP activity and its mRNA expression level could be increased by BMP4 treatment. Previously, we demonstrated that mutation of ERK1/2 phosphorylation sites in Smad5 partially rescued Smad transcriptional activity. However, fibroblast growth factor2-suppressed ALP activity could not be rescued similarly by introduction of Smad5 mutant in MC3T3-E1. These results prompted us to further evaluate the effect of BMP4-stimulated Smad transcriptional activity on ALP expression in this study.展开更多
Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery.Understanding the mechanisms of liver ischemia reperfusion injury(IRI) and developing strategies to counteract this ...Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery.Understanding the mechanisms of liver ischemia reperfusion injury(IRI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation,as well as expanding the potential pool of usable donor grafts.The initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes,increased apoptosis and acute inflammatory changes with increased hepatocyte necrosis.Some adaptive pathways are activated during reperfusion that reduce the reperfusion injury.IRI involves a complex interplay between neutrophils,natural killer T-cells cells,CD4+ T cell subtypes,cytokines,nitric oxide synthases,haem oxygenase-1,survival kinases such as the signal transducer and activator of transcription,Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ pathways.Transgenic animals,particularly genetic knockout models,have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological studies.Targeted disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same protein.This article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI.展开更多
Objective:The anti-inflammatory effects of Ecklonia cava(EC)and its mechanism of action were examined in phorbol-12 myristate 13-acetate(30 nmol/L)and A23187(1μmol/L)(PMACI)stimulated human mast cell line-1 cells.Met...Objective:The anti-inflammatory effects of Ecklonia cava(EC)and its mechanism of action were examined in phorbol-12 myristate 13-acetate(30 nmol/L)and A23187(1μmol/L)(PMACI)stimulated human mast cell line-1 cells.Methods:Nitric oxide content,inducible nitric oxide synthase and cyclooxygenase-2 protein expression,pro-inflammatory cytokines including IL-1β,TNF-α,and IL-6 mRNA and protein expressions were determined.In addition,extracellular regulated protein kinases/mitogen-activated protein kinase(ERK/MAPK)activation was examined.Results:EC dose-dependently suppressed inducible nitric oxide synthase and cyclooxygenase-2 protein expression and subsequently it reduces nitric oxide content in PMACI stimulated human mast cell line-1 cells.EC dose-dependently inhibited the mRNA as well as protein expression of TNF-α,IL—1β,and TL-6 in the PMACI stimulated human mast cell line-1 cells without any cytotoxic effect.Furthermore,EC significantly inhibited PMACI induced phosphorylation of ERK1/2 in a dose-dependent manner without affecting the total protein levels.Conclusions:EC exert its anti-inflammatory actions via inhibition of ERK/MAPK signalling pathway,suggesting that EC is a potent and efficacious anti-inflammatory agent for mast cellmediated inflammatory diseases.展开更多
Necrotrophic fungi, being the largest class of fungal plant pathogens, pose a serious economic problem to crop production. Nitric oxide （NO） is an essential regulatory molecule in plant immunity in synergy with reac...Necrotrophic fungi, being the largest class of fungal plant pathogens, pose a serious economic problem to crop production. Nitric oxide （NO） is an essential regulatory molecule in plant immunity in synergy with reactive oxygen species （ROS）. Most experimental data available on the roles of NO and ROS during plant-pathogen interactions are from studies of infections by potential biotrophic pathogens, including bacteria and viruses. However, there are several arguments about the role of ROS in defense responses during plants and necrotrophic pathogens interaction and little is known about the role of NO as a counterpart of ROS in disease resistance to necrotrophic pathogens. This review focuses on the recent knowledge about the role of oxidative burst in plant defense response to necrotrophic fungi.展开更多
Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. In...Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-7 (BMP-7) and B-cell lymphoma 2 (Bcl-2) are surrogate markers of renal tubular epithelial regeneration and subsequent recovery of renal function following ATN. Methods: Serum creatinine (Scr) and blood urea nitrogen (BUN), as well as expression of iNOS, BMP-7 and Bcl-2 in gentamycin-induced ATN rat kidneys was investigated after human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation. Immunohistochemical staining was performed in 3 groups of rats: gentamycin-induced ATN treated with HUC-MSC, gentamycin-induced ATN without HUC-MSC, and untreated rats not receiving any treatments. Results: HUC-MSC transplantation led to a reduction in Scr and BUN in the kidneys of rats with gentamycin-induced ATN. Expression of iNOS in the HUC-MSC treated group occurred later and the expression levels were much lower during gentamycin-induced ATN compared to rats with ATN that were not treated with HUC-MSC. The expression of BMP-7 and Bcl-2 in the MSC-transplanted group was significantly increased compared to both control groups of rats with injured and healthy renal tubules. Conclusions: HUC-MSCs induce renal protection in a rat model of gentamycin-induced ATN, which is associated with reduced iNOS expression and up-regulation of Bcl-2 and BMP-7.展开更多
Mitogen-activated protein kinases(MPKs)play essential roles in guard cell signaling,but whether MPK cascades participate in guard cell ethylene signaling and interact with hydrogen peroxide(H2O2),nitric oxide(NO),and ...Mitogen-activated protein kinases(MPKs)play essential roles in guard cell signaling,but whether MPK cascades participate in guard cell ethylene signaling and interact with hydrogen peroxide(H2O2),nitric oxide(NO),and ethylene-signaling components remain unclear.Here,we report that ethylene activated MPK3 and MPK6 in the leaves of wild-type Arabidopsis thaliana as well as ethylene insensitive2(ein2),ein3,nitrate reductase1(nia1),and nia2 mutants,but this effect was impaired in ethylene response1(etr1),nicotinamide adenine dinucleotide phosphate oxidase AtrbohF,mpk kinase1(mkk1),and mkk3 mutants.By contrast,the constitutive triple response1(ctr1)mutant had constitutively active MPK3 and MPK6.Yeast two-hybrid,bimolecular fluorescence complementation,and pull-down assays indicated that MPK3 and MPK6 physically interacted with MKK1,MKK3,and the C-terminal region of EIN2(EIN2 CEND).mkk1,mkk3,mpk3,and mpk6 mutants had typical levels of ethylene-induced H2O2 generation but impaired ethylene-induced EIN2 CEND cleavage and nuclear translocation,EIN3 protein accumulation,NO production in guard cells,and stomatal closure.These results show that the MKK1/3–MPK3/6 cascade mediates ethylene-induced stomatal closure by functioning downstream of ETR1,CTR1,and H2O2 to interact with EIN2,thereby promoting EIN3 accumulation and EIN3-dependent NO production in guard cells.展开更多
Plants have evolved intricate signaling cascades to rapidly and effectively respond to biotic and abiotic challenges. The precise timing of these responses enables optimal resource reallocation to maintain the balance...Plants have evolved intricate signaling cascades to rapidly and effectively respond to biotic and abiotic challenges. The precise timing of these responses enables optimal resource reallocation to maintain the balance between stress adaptation and growth. Thus, an in-depth understanding of the immediate and long-term mechanisms regulating resource allocation is critical in deciphering how plants withstand environmental challenges. To date however, understanding of this tradeoff has focused on the amplitude of long-term responses, rather than the timing of rapid stress responses. This review presents current knowledge on kinetics of secondary messengers involved in regulation of rapid and general stress responses, followed by rapid stress responsive transduction machinery, and finally the transcriptional response of a functional general stress responsive cis-element. Within this context we discuss the role of timing of initial peak activation and later oscillating peak responses, and explore hormonal and stress signaling crosstalk confounding greater understanding of these cascades.展开更多
文摘Background Estrogen deficiency results in loss of bone mass compounds with estrogen-like activity that bind to estrogen receptors effect of the phytoestrogen puerarin on adult mouse osteoblasts. Methods Osteoblast cells were harvested from 8-month old female Phytoestrogens are plant-derived non-steroidal The main aim of this study was to investigate the mprinting control region （ICR） mice. The effects of puerarin stimulation on the proliferation, differentiation and maturation of osteoblasts were examined. The production of nitric oxide （NO） and the expression of bone morphogenetic protein-2 （BMP-2）, SMAD4, mitogen-activated protein kinases （MAPK）, core binding factor all runt-related transcription factor 2 （Cbfal/Runx2）, osteoprotegerin （OPG）, and receptor activator of NF-KB ligand （RANKL） genes were analyzed. The activation of signal pathways was further confirmed by specific pathway inhibitors. Results The osteoblast viability reached its maximum at 10-8 mol/L puerarin. At this concentration, puerarin increases the proliferation and matrix mineralization of osteoblasts and promotes NO synthesis. With 108 mol/L puerarin treatment, BMP-2, SMAD4, Cbfal/Runx2, and OPG gene expression were up-regulated, while the RANKL gene expression is down-regulated. Concurrent treatment involving the （bone morphogenetic protein） BMP antagonist Noggin or the NOS inhibitor L-NAME diminishes puerarin induced cell proliferation, Alkaline phosphatase （ALP） activity, NO production, as well as the BMP-2, SMAD4, Cbfal/Runx2, OPG, and RANKL gene expression. Conclusions In this in vitro study, we demonstrate that puerarin is a bone anabolic agent that exerts its osteogenic effects through the induction of BMP-2 and NO synthesis, subsequently regulating Cbfal/Runx2, OPG, and RANKL gene expression. This effect may contribute to its induction of osteoblast proliferation and differentiation, resulting in bone formation.
基金supported by the National Natural Science Foundation of China,Nos. 82071556 (to WM), 81873793 (to WM), 82001198 (to YQZ), 82101310 (to DQL)the National Key Research and Development Program of China,No. 2020YFC2005300 (to WM)。
文摘Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.
基金This work was supported by a grant from the National 863 Program (No. 2003AA205170).
文摘Bone morphogenetic proteins （BMPs） induce ectopic bone formation and promote osteoblast differentiation. It has been documented that Smad transcriptional factors function as primary mediators of BMPs activity. Receptor-regulated Smad （Smad1, 5, 8） could be phosphorylated by activated BMPR-I and form complex with Smad4. The Smad complex translocates to the nucleus and regulate target gene transcription. Recently, several reports suggested that Mitogen-Activated Protein Kinase （MAPK） signaling pathways could be initiated downstream of the BMP receptor complex. Alkaline phosphatase （ALP） is an early marker of osteoblast differentiation Both ALP activity and its mRNA expression level could be increased by BMP4 treatment. Previously, we demonstrated that mutation of ERK1/2 phosphorylation sites in Smad5 partially rescued Smad transcriptional activity. However, fibroblast growth factor2-suppressed ALP activity could not be rescued similarly by introduction of Smad5 mutant in MC3T3-E1. These results prompted us to further evaluate the effect of BMP4-stimulated Smad transcriptional activity on ALP expression in this study.
文摘Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery.Understanding the mechanisms of liver ischemia reperfusion injury(IRI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation,as well as expanding the potential pool of usable donor grafts.The initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes,increased apoptosis and acute inflammatory changes with increased hepatocyte necrosis.Some adaptive pathways are activated during reperfusion that reduce the reperfusion injury.IRI involves a complex interplay between neutrophils,natural killer T-cells cells,CD4+ T cell subtypes,cytokines,nitric oxide synthases,haem oxygenase-1,survival kinases such as the signal transducer and activator of transcription,Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ pathways.Transgenic animals,particularly genetic knockout models,have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological studies.Targeted disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same protein.This article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI.
基金supported by a grant from the 2013 Fundamental R&D Program of Hanseo University
文摘Objective:The anti-inflammatory effects of Ecklonia cava(EC)and its mechanism of action were examined in phorbol-12 myristate 13-acetate(30 nmol/L)and A23187(1μmol/L)(PMACI)stimulated human mast cell line-1 cells.Methods:Nitric oxide content,inducible nitric oxide synthase and cyclooxygenase-2 protein expression,pro-inflammatory cytokines including IL-1β,TNF-α,and IL-6 mRNA and protein expressions were determined.In addition,extracellular regulated protein kinases/mitogen-activated protein kinase(ERK/MAPK)activation was examined.Results:EC dose-dependently suppressed inducible nitric oxide synthase and cyclooxygenase-2 protein expression and subsequently it reduces nitric oxide content in PMACI stimulated human mast cell line-1 cells.EC dose-dependently inhibited the mRNA as well as protein expression of TNF-α,IL—1β,and TL-6 in the PMACI stimulated human mast cell line-1 cells without any cytotoxic effect.Furthermore,EC significantly inhibited PMACI induced phosphorylation of ERK1/2 in a dose-dependent manner without affecting the total protein levels.Conclusions:EC exert its anti-inflammatory actions via inhibition of ERK/MAPK signalling pathway,suggesting that EC is a potent and efficacious anti-inflammatory agent for mast cellmediated inflammatory diseases.
基金supported by the National High Technology Research and Development Program of China(2011AA10A205)
文摘Necrotrophic fungi, being the largest class of fungal plant pathogens, pose a serious economic problem to crop production. Nitric oxide （NO） is an essential regulatory molecule in plant immunity in synergy with reactive oxygen species （ROS）. Most experimental data available on the roles of NO and ROS during plant-pathogen interactions are from studies of infections by potential biotrophic pathogens, including bacteria and viruses. However, there are several arguments about the role of ROS in defense responses during plants and necrotrophic pathogens interaction and little is known about the role of NO as a counterpart of ROS in disease resistance to necrotrophic pathogens. This review focuses on the recent knowledge about the role of oxidative burst in plant defense response to necrotrophic fungi.
文摘Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-7 (BMP-7) and B-cell lymphoma 2 (Bcl-2) are surrogate markers of renal tubular epithelial regeneration and subsequent recovery of renal function following ATN. Methods: Serum creatinine (Scr) and blood urea nitrogen (BUN), as well as expression of iNOS, BMP-7 and Bcl-2 in gentamycin-induced ATN rat kidneys was investigated after human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation. Immunohistochemical staining was performed in 3 groups of rats: gentamycin-induced ATN treated with HUC-MSC, gentamycin-induced ATN without HUC-MSC, and untreated rats not receiving any treatments. Results: HUC-MSC transplantation led to a reduction in Scr and BUN in the kidneys of rats with gentamycin-induced ATN. Expression of iNOS in the HUC-MSC treated group occurred later and the expression levels were much lower during gentamycin-induced ATN compared to rats with ATN that were not treated with HUC-MSC. The expression of BMP-7 and Bcl-2 in the MSC-transplanted group was significantly increased compared to both control groups of rats with injured and healthy renal tubules. Conclusions: HUC-MSCs induce renal protection in a rat model of gentamycin-induced ATN, which is associated with reduced iNOS expression and up-regulation of Bcl-2 and BMP-7.
基金supported by the National Natural Science Foundation of China(31570397,31870375)the Natural Science Research Plan of Shaanxi Province of China(2016JZ008)the Excellent Doctoral Dissertation Project of Shaanxi Normal University(2017TS037).
文摘Mitogen-activated protein kinases(MPKs)play essential roles in guard cell signaling,but whether MPK cascades participate in guard cell ethylene signaling and interact with hydrogen peroxide(H2O2),nitric oxide(NO),and ethylene-signaling components remain unclear.Here,we report that ethylene activated MPK3 and MPK6 in the leaves of wild-type Arabidopsis thaliana as well as ethylene insensitive2(ein2),ein3,nitrate reductase1(nia1),and nia2 mutants,but this effect was impaired in ethylene response1(etr1),nicotinamide adenine dinucleotide phosphate oxidase AtrbohF,mpk kinase1(mkk1),and mkk3 mutants.By contrast,the constitutive triple response1(ctr1)mutant had constitutively active MPK3 and MPK6.Yeast two-hybrid,bimolecular fluorescence complementation,and pull-down assays indicated that MPK3 and MPK6 physically interacted with MKK1,MKK3,and the C-terminal region of EIN2(EIN2 CEND).mkk1,mkk3,mpk3,and mpk6 mutants had typical levels of ethylene-induced H2O2 generation but impaired ethylene-induced EIN2 CEND cleavage and nuclear translocation,EIN3 protein accumulation,NO production in guard cells,and stomatal closure.These results show that the MKK1/3–MPK3/6 cascade mediates ethylene-induced stomatal closure by functioning downstream of ETR1,CTR1,and H2O2 to interact with EIN2,thereby promoting EIN3 accumulation and EIN3-dependent NO production in guard cells.
基金supported by National Institute of Health(R01GM107311)National Science Foundation(IOS1036491 and IOS-1352478)+1 种基金Agriculture experiment station (CA-D-PLB-3510-H) grants awarded to KDsupported by the John F.Steindler Fellowship
文摘Plants have evolved intricate signaling cascades to rapidly and effectively respond to biotic and abiotic challenges. The precise timing of these responses enables optimal resource reallocation to maintain the balance between stress adaptation and growth. Thus, an in-depth understanding of the immediate and long-term mechanisms regulating resource allocation is critical in deciphering how plants withstand environmental challenges. To date however, understanding of this tradeoff has focused on the amplitude of long-term responses, rather than the timing of rapid stress responses. This review presents current knowledge on kinetics of secondary messengers involved in regulation of rapid and general stress responses, followed by rapid stress responsive transduction machinery, and finally the transcriptional response of a functional general stress responsive cis-element. Within this context we discuss the role of timing of initial peak activation and later oscillating peak responses, and explore hormonal and stress signaling crosstalk confounding greater understanding of these cascades.
