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Hepatocyte growth factor (HGF) induces a protective response against toxicity induced by ethanol and acetaldehyde in pancreatic cell lines
S174
Abstracts / Toxicology Letters 259S (2016) S73–S247
PP17.4 The role of autophagy during cadmium induced apoptosis in rat renal tubular epithelial cells
PP17.5 The systems toxicology challenge: Marker of exposure response identification in blood
G. Liu 1,2 , J.C. Bian 1,2 , X.Z. Liu 1,2 , Y. Yuan 1,2 , J.H. Gu 1,2 , H. Zou 1,2 , Z.P. Liu 1,2
C. Poussin, V. Belcastro, S. Boué, F. Martin, A. Sewer, B. Titz, L. Cannesson, M.C. Peitsch, J. Hoeng
1 College of Veterinary Medicine, Yangzhou University, Yangzhou, People’s Republic of China 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China
PMI R&D, Philip Morris Products S.A. (part of Philip Morris International group of companies), Neuchatel, Switzerland
Introduction: Caspases play a crucial role in apoptosis, stress factors converge on mitochondria to induce mitochondrial membrane permeabilization, which can trigger release of apoptogenic signaling molecules, such as cytochrome c (cyt c), to active caspase cascade signals includes caspase-9 and caspase-3, and then induce apoptosis. Previous studies have demonstrated that cadmium (Cd) could induce apoptosis in primary cultures of rat proximal tubular cells (rPT cells) exposed to Cd for 12 h. And some studies confirmed that viability of cells, treated with 10 M Cd for 0–6 h, were increased significantly. It had been reported that internal stressinduced autophagy was increased during 0–12 h, and our group results found the autophagy level was highest in 4–6 h, and it was decreased after 6 h. The link between autophagy and apoptosis had been reported early. However, the precise molecular mechanisms underlying Cd-induced autophagy and its role during cadmiuminduced apoptosis are largely unknown. Objective: The purpose of this study was to further clarify the underlying mechanism of Cd-induced autophagy and relationship between autophagy and apoptosis. Materials and methods: FITC Annexin V Apoptosis Detection Kit I was used to detect apoptosis with flow cytometer; cyt c, cleaved caspase-9, -3, LC3, Beclin-1, Atg7 and p62 antibodies were used to detect protein level with western blot; MDC fluorescence probe was used to detect autophagy level; Rapamycin (RAP) and chloroquine (CQ) was used to promote or inhibit autophagy; And siRNA Beclin-1 and Lipofectamine® 3000 Reagent Protocol were used to knockdown Beclin-1 protein. Results: Apoptosis rate of NRK-52E cells and rPT cells was decreased in a dose-dependent manner when exposed to Cd for 6 h, which were also demonstrated by reducing the release of mitochondrial (cyt c) and activation of caspase-3; while apoptosis rate was increased at 12 h, which was dependent on the mitochondrial apoptotic pathway. MDC staining results showed that the level of autophagy was increased in a dose-dependent manner when treated with Cd by 6 h and the autophagy level decreased at 12 h. Autophagy was initiated by deacetylated LC3, which transfers from the nucleus to the cytoplasm, then regulated by Bcelin-1, autophagy gene 7 (Atg7) and p62. It is interesting that Cd stimulated the formation of autophagosome, while inhibited the degradation function of lysosomes. Rapamycin (RAP) promoted the autophagy level accompanied by protecting cells from apoptosis, and 3-MA caused apoptosis rate increased, while chloroquine (CQ) could not influence cells apoptosis. siRNA Beclin-1 significantly induced the activation of caspase-3 and increasing the cells apoptosis rate. Conclusions: Cd induced apoptosis could prevent by autophagy which play a protective role against apoptosis. And this role was efficient before lysosome and Bcelin-1 is a pivotal factor to influence apoptosis induced by Cd in rat renal tubular epithelial cells. http://dx.doi.org/10.1016/j.toxlet.2016.07.414
Introduction: Humans are constantly exposed to chemicals (e.g. pollutants, cigarette smoke) that can trigger molecular changes and be harmful for their organism. Risk assessment in the context of 21st century toxicology relies on the elucidation of mechanisms of toxicity and the identification of markers of exposure response. Objective: For that purpose, datasets using high-throughput technologies are generated from various biological samples after the exposure of cells or subjects to individual or mixture of chemicals. The development of relevant computational approaches for the analysis and integration of these large-scale data remains challenging and requires qualitative and quantitative evaluation. Materials and methods: The scope of sbv IMPROVER (Industrial Methodology for Process Verification in Research; www. sbvimprover.com) is the verification of methods and concepts in systems biology research via challenges proposed to the scientific community. The latest sbv IMPROVER computational challenge (Fall 2015–Spring 2016) aimed to address questions on (i) the identification of exposure response markers in human blood enabling to discriminate between exposed and non-exposed subjects as well as (ii) the translatability of those markers between species. Participants were provided with human and mouse blood gene expression data sets to develop gene signature-based models for exposure group class prediction. Results: Anonymized submissions were scored by comparing the predictions to the “Gold Standard” (true class labels) using specific metrics to identify the most performant computational methods. Conclusion: The outcome of the computational challenge is summarized in this poster. Financial support: Philip Morris International. http://dx.doi.org/10.1016/j.toxlet.2016.07.415 PP17.6 Hepatocyte growth factor (HGF) induces a protective response against toxicity induced by ethanol and acetaldehyde in pancreatic cell lines J.I. Rodriguez-Ochoa 1 , M. Palestino-Dominguez 1 , M. Vergara-Mendoza 1 , M. Pelaez-Luna 2 , J.U. Marquardt 3 , M.C. Gutierrez-Ruiz 1 , R.U. Miranda 1 , L.E. Gomez-Quiroz 1 1 Departamento de Ciencias de la Salud, Universidad Autonoma Metropolitana Iztapalapa, Mexico City, Mexico 2 Departamento de Gastroenterología INCMNSZ, Mexico City, Mexico 3 Department of Medicine I and Core Facility Bioinformatics, Johannes Gutenberg University, Mainz, Germany
Introduction: Alcohol is the main toxic ingested by recreation in spite of its well-known toxic effects in many organs including the liver and pancreas. Alcohol and acetaldehyde, target practically all cell types in the pancreas inducing inflammation that eventually could conduce to fibrosis and cancer. HGF has been positioned as a master regulator of the oxidative stress by activating canonical
Abstracts / Toxicology Letters 259S (2016) S73–S247
signaling pathways such as Akt, Erk1/2 and transcription factors such as NF-B, STAT3 or Nrf2. Objective: To address the effect of HGF against ethanol- and acetaldehyde-induced toxicity in RINm5F and CAPAN-1 pancreatic cell lines. Material and methods: RINm5F and CAPAN-1 cells were treated with 100 mM ethanol or 200 M acetaldehyde at different times of incubation in the presence or not of HGF (50 ng/ml). Cell viability was measured by CCK-8 kit and cell functionality by neutral red assay, apoptosis was addressed by acridine orange staining and the content of key cellular damage and survival proteins were studied by Western blotting. Results: Both toxics induced cell dysfunction, judged by neutral red assay, this effect was prevented by HGF. The protective effect was related to the expression of antioxidant enzymes such as GSTM, ␥-GCS and SOD1 in both cells lines RINm5F and CAPAN-1. In order to figure out the signaling pathways involved in this response we studied the activation of Erk1/2, Akt, Nrf2 and p38. Erk 1/2 and Akt were activated by HGF in both cell lines. In addition, this effect was associated to a decreased in apoptosis judged by a decrease in apoptotic cells and the activation of caspase 3. Conclusion: HGF exerted a protective mechanism in pancreatic cells by the modulation of antioxidants proteins by a mechanism mediated by Erk 1/2 and Akt and the activation of Nrf2, this could represent a promising molecular target for the treatment of alcoholic pancreatic disease. Financial support: Conacyt 252942, 222578. http://dx.doi.org/10.1016/j.toxlet.2016.07.416 PP17.7 NADPH oxidase (NOX) 1 mediates cigarette smoke-induced superoxide generation in rat vascular smooth muscle cells Kyung-Hwa Chang, Jung-Min Park, Moo-Yeol Lee College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of Korea Introduction: Smoking is a well-established risk factor for cardiovascular diseases. Although multiple mechanisms were reported, one of the common etiological factors is the oxidative stress and NADPH oxidase (NOX) has been suggested as a potential culprit for such oxidative stress. Objective: Cigarette smoke (CS)-stimulated superoxide production was characterized in vascular smooth muscle cells (VSMC). Materials and methods: CS was prepared as forms of cigarette smoke extract (CSE) and total particulate matters (TPM) which are CS trapped in phosphate-buffered saline and on Cambridge filter pad, respectively. Dihydroethidium (DHE) and 2-(4-iodophenyl)3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) were used for superoxide detection in cultured VSMC. Results: Both CSE and TPM generated superoxide in VSMC culture system by stimulating cells to produce superoxide and directly producing superoxide in extracellular aqueous solution. NOX, specifically NOX1 was identified as a major cellular source for superoxide through the experiments using NOX inhibitors such as diphenyleneiodonium (DPI) and VAS2870 and NOX-silenced VSMC. Cytotoxicity of CSE was prevented by NOX inhibitors and a superoxide dismutase mimetic TEMPOL, indicating that NOX1-produced superoxide contributes to cytotoxicity. Conclusions: Since NOX1 is known to mediate diverse pathological processes in vascular system, NOX1 may be a critical effecter in cardiovascular toxicity caused by smoking.
S175
Financial support: This research was supported by a grant (14182MFDS977) from Ministry of Food and Drug Safety in 2016. http://dx.doi.org/10.1016/j.toxlet.2016.07.417 PP17.8 MAP kinases are essential for the benzo[a]pyrene metabolism in BEAS-2B cells G.G. Vázquez 1 , L. Rocha 2 , M. Rodríguez 3 , J. Rubio 1 1 Genomic Medicine and Environmental Toxicology Department, Mexico City, Mexico 2 Biotechnology and Molecular Biology Department, Biomedical Research Institute, UNAM, C.U., Mexico City, Mexico 3 Biomedicine Unit, FES Iztacala, UNAM, Mexico
Introduction: Benzo[a]pyrene (b[a]p), as the first identified carcinogenic component of polycyclic aromatic hydrocarbons (PAH), is the most extensively studied carcinogen in cigarette smoke and has been regarded as a critical mediator of lung cancer for a long time due by its bioactivation through the Aryl Hydrocarbon Receptor (AhR) signaling pathway to benzo[a]pyrene diol epoxide (B[a]PDE). Studies suggest that PAH can activate the Mitogen Activated Protein Kinases (MAPK), however, their involvement in b[a]p metabolism and toxicity remains unknown. Cellular alterations induced by b[a]p are complex and they may be mediated by more than one signaling pathway, so it is essential to know which pathways are involved in b[a]p metabolism to a better understanding of the molecular basis of some diseases like cancer. Objectives: The aim of this work is to determine the involvement of both ERK and JNK kinases in the metabolism of b[a]p and the production of its toxic effects in normal bronco epithelial lung cells (BEAS-2B). Materials and methods: BEAS-2B cell line was employed to determine whether the MAP kinases are involved in the metabolism of b[a]p and in the production of cellular damage. We exposed cells to b[a]p and/or ERK and JNK inhibitors in order to quantify the level of CYP450, ERK and JNK proteins and the production of benzo[a]pyrene diolepoxide adducts in DNA. Results: B[a]p is not cytotoxic to the BEAS-2B cells at relatively low concentrations. B[a]p enhances CYP1A1 transcription and increases their protein concentration. Additionally, b[a]p promotes the ERK and JNK phosphorylation. On the other hand, inhibition of ERK decreases the CYP1A1 transcription and protein quantity. Conclusions: These data suggest a crosstalk between AhR and MAPK pathways, which is essential in the modulation of AhR pathway in the metabolism of b[a]p in BEAS 2B cells. Financial support: CONACYT scholarship No. 233838. http://dx.doi.org/10.1016/j.toxlet.2016.07.418 PP17.9 1,4-Naphthoquinone-mediated activation of the HSP90/HSF1 signal transduction pathway and its negative regulation by reactive sulfur species in human A431 cells T. Unoki 1 , Y. Shinkai 1 , L. Sha 2 , R. Hirose 2 , Y. Kumagai 1 1 2
Faculty of Medicine, University of Tsukuba, Tsukuba, Japan Human Biology Program, University of Tsukuba, Tsukuba, Japan
Introduction: 1,4-Naphthoquinone (1,4-NQ) is found as an atmospheric electrophile that is readily able to modify protein nucleophiles. Covalent modification of cellular proteins by elec-
Abstracts / Toxicology Letters 259S (2016) S73–S247
PP17.4 The role of autophagy during cadmium induced apoptosis in rat renal tubular epithelial cells
PP17.5 The systems toxicology challenge: Marker of exposure response identification in blood
G. Liu 1,2 , J.C. Bian 1,2 , X.Z. Liu 1,2 , Y. Yuan 1,2 , J.H. Gu 1,2 , H. Zou 1,2 , Z.P. Liu 1,2
C. Poussin, V. Belcastro, S. Boué, F. Martin, A. Sewer, B. Titz, L. Cannesson, M.C. Peitsch, J. Hoeng
1 College of Veterinary Medicine, Yangzhou University, Yangzhou, People’s Republic of China 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China
PMI R&D, Philip Morris Products S.A. (part of Philip Morris International group of companies), Neuchatel, Switzerland
Introduction: Caspases play a crucial role in apoptosis, stress factors converge on mitochondria to induce mitochondrial membrane permeabilization, which can trigger release of apoptogenic signaling molecules, such as cytochrome c (cyt c), to active caspase cascade signals includes caspase-9 and caspase-3, and then induce apoptosis. Previous studies have demonstrated that cadmium (Cd) could induce apoptosis in primary cultures of rat proximal tubular cells (rPT cells) exposed to Cd for 12 h. And some studies confirmed that viability of cells, treated with 10 M Cd for 0–6 h, were increased significantly. It had been reported that internal stressinduced autophagy was increased during 0–12 h, and our group results found the autophagy level was highest in 4–6 h, and it was decreased after 6 h. The link between autophagy and apoptosis had been reported early. However, the precise molecular mechanisms underlying Cd-induced autophagy and its role during cadmiuminduced apoptosis are largely unknown. Objective: The purpose of this study was to further clarify the underlying mechanism of Cd-induced autophagy and relationship between autophagy and apoptosis. Materials and methods: FITC Annexin V Apoptosis Detection Kit I was used to detect apoptosis with flow cytometer; cyt c, cleaved caspase-9, -3, LC3, Beclin-1, Atg7 and p62 antibodies were used to detect protein level with western blot; MDC fluorescence probe was used to detect autophagy level; Rapamycin (RAP) and chloroquine (CQ) was used to promote or inhibit autophagy; And siRNA Beclin-1 and Lipofectamine® 3000 Reagent Protocol were used to knockdown Beclin-1 protein. Results: Apoptosis rate of NRK-52E cells and rPT cells was decreased in a dose-dependent manner when exposed to Cd for 6 h, which were also demonstrated by reducing the release of mitochondrial (cyt c) and activation of caspase-3; while apoptosis rate was increased at 12 h, which was dependent on the mitochondrial apoptotic pathway. MDC staining results showed that the level of autophagy was increased in a dose-dependent manner when treated with Cd by 6 h and the autophagy level decreased at 12 h. Autophagy was initiated by deacetylated LC3, which transfers from the nucleus to the cytoplasm, then regulated by Bcelin-1, autophagy gene 7 (Atg7) and p62. It is interesting that Cd stimulated the formation of autophagosome, while inhibited the degradation function of lysosomes. Rapamycin (RAP) promoted the autophagy level accompanied by protecting cells from apoptosis, and 3-MA caused apoptosis rate increased, while chloroquine (CQ) could not influence cells apoptosis. siRNA Beclin-1 significantly induced the activation of caspase-3 and increasing the cells apoptosis rate. Conclusions: Cd induced apoptosis could prevent by autophagy which play a protective role against apoptosis. And this role was efficient before lysosome and Bcelin-1 is a pivotal factor to influence apoptosis induced by Cd in rat renal tubular epithelial cells. http://dx.doi.org/10.1016/j.toxlet.2016.07.414
Introduction: Humans are constantly exposed to chemicals (e.g. pollutants, cigarette smoke) that can trigger molecular changes and be harmful for their organism. Risk assessment in the context of 21st century toxicology relies on the elucidation of mechanisms of toxicity and the identification of markers of exposure response. Objective: For that purpose, datasets using high-throughput technologies are generated from various biological samples after the exposure of cells or subjects to individual or mixture of chemicals. The development of relevant computational approaches for the analysis and integration of these large-scale data remains challenging and requires qualitative and quantitative evaluation. Materials and methods: The scope of sbv IMPROVER (Industrial Methodology for Process Verification in Research; www. sbvimprover.com) is the verification of methods and concepts in systems biology research via challenges proposed to the scientific community. The latest sbv IMPROVER computational challenge (Fall 2015–Spring 2016) aimed to address questions on (i) the identification of exposure response markers in human blood enabling to discriminate between exposed and non-exposed subjects as well as (ii) the translatability of those markers between species. Participants were provided with human and mouse blood gene expression data sets to develop gene signature-based models for exposure group class prediction. Results: Anonymized submissions were scored by comparing the predictions to the “Gold Standard” (true class labels) using specific metrics to identify the most performant computational methods. Conclusion: The outcome of the computational challenge is summarized in this poster. Financial support: Philip Morris International. http://dx.doi.org/10.1016/j.toxlet.2016.07.415 PP17.6 Hepatocyte growth factor (HGF) induces a protective response against toxicity induced by ethanol and acetaldehyde in pancreatic cell lines J.I. Rodriguez-Ochoa 1 , M. Palestino-Dominguez 1 , M. Vergara-Mendoza 1 , M. Pelaez-Luna 2 , J.U. Marquardt 3 , M.C. Gutierrez-Ruiz 1 , R.U. Miranda 1 , L.E. Gomez-Quiroz 1 1 Departamento de Ciencias de la Salud, Universidad Autonoma Metropolitana Iztapalapa, Mexico City, Mexico 2 Departamento de Gastroenterología INCMNSZ, Mexico City, Mexico 3 Department of Medicine I and Core Facility Bioinformatics, Johannes Gutenberg University, Mainz, Germany
Introduction: Alcohol is the main toxic ingested by recreation in spite of its well-known toxic effects in many organs including the liver and pancreas. Alcohol and acetaldehyde, target practically all cell types in the pancreas inducing inflammation that eventually could conduce to fibrosis and cancer. HGF has been positioned as a master regulator of the oxidative stress by activating canonical
Abstracts / Toxicology Letters 259S (2016) S73–S247
signaling pathways such as Akt, Erk1/2 and transcription factors such as NF-B, STAT3 or Nrf2. Objective: To address the effect of HGF against ethanol- and acetaldehyde-induced toxicity in RINm5F and CAPAN-1 pancreatic cell lines. Material and methods: RINm5F and CAPAN-1 cells were treated with 100 mM ethanol or 200 M acetaldehyde at different times of incubation in the presence or not of HGF (50 ng/ml). Cell viability was measured by CCK-8 kit and cell functionality by neutral red assay, apoptosis was addressed by acridine orange staining and the content of key cellular damage and survival proteins were studied by Western blotting. Results: Both toxics induced cell dysfunction, judged by neutral red assay, this effect was prevented by HGF. The protective effect was related to the expression of antioxidant enzymes such as GSTM, ␥-GCS and SOD1 in both cells lines RINm5F and CAPAN-1. In order to figure out the signaling pathways involved in this response we studied the activation of Erk1/2, Akt, Nrf2 and p38. Erk 1/2 and Akt were activated by HGF in both cell lines. In addition, this effect was associated to a decreased in apoptosis judged by a decrease in apoptotic cells and the activation of caspase 3. Conclusion: HGF exerted a protective mechanism in pancreatic cells by the modulation of antioxidants proteins by a mechanism mediated by Erk 1/2 and Akt and the activation of Nrf2, this could represent a promising molecular target for the treatment of alcoholic pancreatic disease. Financial support: Conacyt 252942, 222578. http://dx.doi.org/10.1016/j.toxlet.2016.07.416 PP17.7 NADPH oxidase (NOX) 1 mediates cigarette smoke-induced superoxide generation in rat vascular smooth muscle cells Kyung-Hwa Chang, Jung-Min Park, Moo-Yeol Lee College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of Korea Introduction: Smoking is a well-established risk factor for cardiovascular diseases. Although multiple mechanisms were reported, one of the common etiological factors is the oxidative stress and NADPH oxidase (NOX) has been suggested as a potential culprit for such oxidative stress. Objective: Cigarette smoke (CS)-stimulated superoxide production was characterized in vascular smooth muscle cells (VSMC). Materials and methods: CS was prepared as forms of cigarette smoke extract (CSE) and total particulate matters (TPM) which are CS trapped in phosphate-buffered saline and on Cambridge filter pad, respectively. Dihydroethidium (DHE) and 2-(4-iodophenyl)3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) were used for superoxide detection in cultured VSMC. Results: Both CSE and TPM generated superoxide in VSMC culture system by stimulating cells to produce superoxide and directly producing superoxide in extracellular aqueous solution. NOX, specifically NOX1 was identified as a major cellular source for superoxide through the experiments using NOX inhibitors such as diphenyleneiodonium (DPI) and VAS2870 and NOX-silenced VSMC. Cytotoxicity of CSE was prevented by NOX inhibitors and a superoxide dismutase mimetic TEMPOL, indicating that NOX1-produced superoxide contributes to cytotoxicity. Conclusions: Since NOX1 is known to mediate diverse pathological processes in vascular system, NOX1 may be a critical effecter in cardiovascular toxicity caused by smoking.
S175
Financial support: This research was supported by a grant (14182MFDS977) from Ministry of Food and Drug Safety in 2016. http://dx.doi.org/10.1016/j.toxlet.2016.07.417 PP17.8 MAP kinases are essential for the benzo[a]pyrene metabolism in BEAS-2B cells G.G. Vázquez 1 , L. Rocha 2 , M. Rodríguez 3 , J. Rubio 1 1 Genomic Medicine and Environmental Toxicology Department, Mexico City, Mexico 2 Biotechnology and Molecular Biology Department, Biomedical Research Institute, UNAM, C.U., Mexico City, Mexico 3 Biomedicine Unit, FES Iztacala, UNAM, Mexico
Introduction: Benzo[a]pyrene (b[a]p), as the first identified carcinogenic component of polycyclic aromatic hydrocarbons (PAH), is the most extensively studied carcinogen in cigarette smoke and has been regarded as a critical mediator of lung cancer for a long time due by its bioactivation through the Aryl Hydrocarbon Receptor (AhR) signaling pathway to benzo[a]pyrene diol epoxide (B[a]PDE). Studies suggest that PAH can activate the Mitogen Activated Protein Kinases (MAPK), however, their involvement in b[a]p metabolism and toxicity remains unknown. Cellular alterations induced by b[a]p are complex and they may be mediated by more than one signaling pathway, so it is essential to know which pathways are involved in b[a]p metabolism to a better understanding of the molecular basis of some diseases like cancer. Objectives: The aim of this work is to determine the involvement of both ERK and JNK kinases in the metabolism of b[a]p and the production of its toxic effects in normal bronco epithelial lung cells (BEAS-2B). Materials and methods: BEAS-2B cell line was employed to determine whether the MAP kinases are involved in the metabolism of b[a]p and in the production of cellular damage. We exposed cells to b[a]p and/or ERK and JNK inhibitors in order to quantify the level of CYP450, ERK and JNK proteins and the production of benzo[a]pyrene diolepoxide adducts in DNA. Results: B[a]p is not cytotoxic to the BEAS-2B cells at relatively low concentrations. B[a]p enhances CYP1A1 transcription and increases their protein concentration. Additionally, b[a]p promotes the ERK and JNK phosphorylation. On the other hand, inhibition of ERK decreases the CYP1A1 transcription and protein quantity. Conclusions: These data suggest a crosstalk between AhR and MAPK pathways, which is essential in the modulation of AhR pathway in the metabolism of b[a]p in BEAS 2B cells. Financial support: CONACYT scholarship No. 233838. http://dx.doi.org/10.1016/j.toxlet.2016.07.418 PP17.9 1,4-Naphthoquinone-mediated activation of the HSP90/HSF1 signal transduction pathway and its negative regulation by reactive sulfur species in human A431 cells T. Unoki 1 , Y. Shinkai 1 , L. Sha 2 , R. Hirose 2 , Y. Kumagai 1 1 2
Faculty of Medicine, University of Tsukuba, Tsukuba, Japan Human Biology Program, University of Tsukuba, Tsukuba, Japan
Introduction: 1,4-Naphthoquinone (1,4-NQ) is found as an atmospheric electrophile that is readily able to modify protein nucleophiles. Covalent modification of cellular proteins by elec-