“有丝分裂”的信息化课堂教学实例

随着信息化时代的到来,信息化教学应运而生,信息技术可实现知识动态化、理实一体化、课堂趣味化、教学灵活化、学习个性化、评价多维化。“有丝分裂”内容抽象难懂,学生较难掌握,学习兴趣不高,但掌握这部分内容对学习整个生物学及后续医学课程至关重要。为提高“有丝分裂”教学质量,应用信息化技术,收到了良好的教学效果,现介绍如下。1教材分析“有丝分裂”为医学生物学基础课程中的内容。医学生物学基础是医学专业的一门公共基础课,采用“十二五”职业教育国家规划教材。

The Change of Microtubule Cytoskeleton in the Stem-Tip Cells of Sugarcane during Mitosis

In order to understand the microtubule change of monocotyls stem-tip during mitosis, the arrangement, transformation of microtubule array and its relation with chromosome movement during mitosis were studied with freezing microtome, indirect immunofluoreseenee, DAPI staining and fluorescence microscopy. The results showed that nucleolus was intact when the cortical microtubules formed; cortical microtubules were changed into phramoplast microtubules bands at mitosis prophase. When phramoplast microtubules came into being, nuclear membrane was ruptured and chromosome was arranged at the position of cell plate ; subsequently, phramoplast microtubules were changed into phragmoplast microtubules, phramoplast microtubules were shortening and microtubules on the sides of cell plate were increasing gradually, during this course sister ehromatid was separated by microtubules at cell plate and tract to the two poles, forming phragmoplast microtubules. Then the nucleolus of two daughter cells formed and separated in the end with the increase of cells numbers. Therefore, cell division orientation could be judged from the arrangement of cell microtubules in different periods in order to understand its growth status.

Involvement of ERK1/2 and p38 MAPK in up-regulation of 14-3-3 protein induced by hydrogen peroxide preconditioning in PC12 cells

Objective To investigate the protective effects of hydrogen peroxide preconditioning （HPP） on the pheochromocytoma （PC12） cells treated with 1-methyl-4-phenylpyridinium （MPP^＋） and to explore the potential mechanisms. Methods The viability and apoptosis of PC 12 cells were determinded by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay and 4′,6′-diamidino-2-phenylindole （DAPI） staining, respectively. The expressions of 14-3-3 protein and phospholylated p38 mitogen-activated protein kinase （MAPK） were determined by Western blot. Enzyme-linked immunosorbent assay （ELISA） was used to measure the activity of extracellular signal-regulated protein kinase 1/2 （ERK1/2）. Results The cell viability decreased and the number of apoptotic cells increased dramatically in MPP^＋ group compared with that in Control group. HPP induced a significant increase in cell viability and a marked decrease in population of apoptotic cells of the MPP^＋- treated PC 12 cells, accompanied with up-regulation of 14-3-3 protein and increase of ERK 1/2 and p38 MAPK activities. The 14-3-3 protein expression was positively correlated with the phosphorylation of ERK1/2. Furthermore, inhibition of the ERK1/2 with PD98059 abolished the 14-3-3 protein up-regulation in PC 12 cells induced by HPP. Conclusion HPP protects PC 12 cells against MPP＋ toxicity by up-regulating 14-3-3 protein expression through the ERK1/2 and p38 MAPK signaling pathways.

Effects of Pb on Growth and Development of Broad Bean Roots

[Objective] This study aimed to investigate the influence of Pb2＋ on the growth and development of broad bean roots. [Method] The effects of Pb2＋ solution of different concentrations on root length, color, bending and mitotic index frequency of root tip cells of broad bean were measured and observed. [Result] Pb2＋ at concentration lower than 20 mg/L promoted the growth and development of roots, increased the cell mitotic indexes, but had little influence on root color and bending. When the Pb2＋ concentration was higher than 20 mg/L, the root growth was inhibited; the root color gradually turned deeper; the roots bended, but the cell mitotic index was decreased. [Conclusion] Pb2＋ promoted the growth of broad bean at low concentration but inhibited the growth at high concentration, and the influence was related to Pb2＋ concentration and time.

Localization of Phosphorylated Histone H3 at Mitosis and Meiosis in Wheat

One of the prominent cell cycle related modifications of histone proteins, whose function is correlated with chromosome condensation, is the phosphorylation of histone H3. Wheat (Triticum aestivum L.) mitotic and meiotic cells were analyzed with indirect immunoflurorescence labeling with an antibody recognizing histone H3 phosphorylated at Serine 10 to study the localization of phosphorylated histone H3 at mitosis and meiosis. Our results showed that, during mitotic division, the phosphoryiation of H3 started from early prophase and vanished at telophase, remaining mainly in the pericentromeric regions at metaphase and anaphase. During meiotic division, phosphorylation of H3 initiated at the transition from leptotene to zygotene and remained uniform, along the chromosomes from prophase I until telophase whereas it showed slightly stronger in the pericentromeric regions than along the chromosome arms from metaphase II until Lelophase II The different patterns of H3 phophorylation at mitosis and meiosis in wheat suggested that this evolutionarily conserved post-translational chromatin modification might be involved in more roles besides chromosome condensation.

Observation of Mitosis and Meiosis in Rice Cells by Simple Squash Method

[Objective] The aim of this study was to establish a feasible squashing technique for chromosome and obtain data of rice chromosome. [Method] With the materials of rice root tips and anther, the specimen was prepared by the modified squash method, and microscopic observation of mitosis and meiosis in rice cells was also carried out. [ Result] Mitosis in rice cells included interphase, prophase, metaphase, anaphase and telophase. Chromosome in metaphase shortened to the minmum, which was a good time for observing and investigating chromosome. However, meiosis in rice cells included meiosis Ⅰ and meiosis Ⅱ. Chromosome replication appeared in meiosis Ⅰ, while cell division only appeared in meiosis Ⅱ. [ Conclusion] The modified squashing technique for rice chromosome can obtain accurate data of rice chromosome, which provides evidence for genetic breeding.

Changes of the Microtubule Arrays During Mitosis in Prothallus Cells of Dryopteris crassirhizoma

Microtubule arrays in prothalli large-vacuolated and meristematic dividing cells of the fern Dryopteris crassirhizoma Nakai were studied using Steedman's wax, indirect immunofluorescence labelling and confocal laser scanning microscopy. Results showed that the use of high paraformaldehyde concentration (8%) allowed good fixation of prothallus cells, which are characterized by numerous (meristematic cells) and big (large-vacuolated cells) vacuoles. Results also plead for the efficiency of Steedman's wax embedding method in: (1) avoiding excessive use of enzyme for digesting cell wall in the process of the microtubule cytoskeleton labelling, (2) minimizing the autofluorescence effect in cells through utilization of alcohol in sample dehydration, and (3) permitting a clear visualization of microtubule patterns during the cell mitosis. Steedman's wax, coupled with immunofluorescence labelling and confocal laser scanning microscopy techniques, allows a good investigation of cell division process in plants by using simple multicellular organisms such as fern prothalli.

MEKK1, MKK1/MKK2 and MPK4 function together in a mitogen-activated protein kinase cascade to regulate innate immunity in plants

Mitogen-activated protein kinase （MAPK） cascades play important roles in regulating plant innate immune responses. In a genetic screen to search for mutants with constitutive defense responses, we identified multiple alleles of mpk4 and mekkl that exhibit cell death and constitutive defense responses. Bimolecular fluorescence complemen- tation （BiFC） analysis showed that both MPK4 and MEKK1 interact with MKK1 and MKK2, two closely related MAPK kinases, mkkl and mkk2 single mutant plants do not have obvious mutant phenotypes. To test whether MKK1 and MKK2 function redundantly, mkkl mkk2 double mutants were generated. The mkkl mkk2 double mutant plants die at seedling stage and the seedling-lethality phenotype is temperature-dependent. Similar to the mpk4 and mekkl mutants, the mkkl mkk2 double mutant seedlings accumulate high levels of H202, display spontaneous cell death, constitutively express Pathogenesis Related （PR） genes and exhibit pathogen resistance. In addition, activation of MPK4 by fig22 is impaired in the mkkl mkk2 double mutants, suggesting that MKK1 and MKK2 function together with MPK4 and MEKK1 in a MAP kinase cascade to negatively regulate innate immune responses in plants.

Inhibitory effect of Polo-like kinase 1 depletion on mitosis and apoptosis of gastric cancer cells

AIM： Polo-like kinase 1 （PLK1） serine/threonine kinase plays a vital role in multiple phases of mitosis in gastric cancer cells. To investigate the effect of PLK1 depletion on mitosis and apoptosis of gastric cancer cells. METHODS： PLK1 expression was blocked by small RNA interference（siRNA）. The expression levels of PLK1, cdc2, cyclin B and caspase 3 were detected by Western blotting. Then, PLK1 depletion, cdc2 activity, cell proliferation, cell cycle phase distribution, mitotic spindle structure, and the rate of apoptosis of the PLK1 knockdown cells were observed. RESULTS： PLK1 gene knockdown was associated with increased cyclin B expression, increased cdc2 activity （but not with the expression levels）, accumulation of gastric cancer cells at G2/M, improper mitotic spindle formation, delayed chromosome separation and delayed or arrested cytokinesis. Moreover, PLK1 depletion in gastric cancer cells was associated with decreased proliferation, attenuated pro-caspase 3 levels and increased apoptosis. CONCLUSION： Blockage of to decreased mitosis or even PLK1 expression may lead apoptosis in gastric cancer cells, indicating that PLK1 may be a valuable therapeutic target for gastric cancer.

Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer

AIM: To investigate the expression of mitogen-activated protein kinases (MAPKs) and its upstream protein kinase in human gastric cancer and to evaluate the relationship between protein levels and clinicopathological parameters. METHODS: Western blot was used to measure the expression of extracellular signal-regulated kinase (ERK)-1, ERK-2, ERK-3, p38 and mitogen or ERK activated protein kinaseMEK-1 proteins in surgically resected gastric carcinoma, adjacent normal mucosa and metastatic lymph nodes from 42 patients. Immunohistochemistry was employed for their localization. RESULTS: Compared with normal tissues, the protein levels of ERK-1 (integral optical density value 159 526?5 760 vs 122 807±65 515, P= 0.001), ERK-2 (168 471±95 051 vs 120 469±72 874, P<0.001), ERK-3 (118 651±71 513 vs 70 934±68 058,P<0.001), P38 (104 776±51 650 vs 82 930±40 392, P= 0.048) and MEK-1 (116 486±45 725 vs 101 434±49 387, P = 0.027) were increased in gastric cancer tissues. Overexpression of ERK-3 was correlated to TNM staging [average ratio of integral optic density (IOD)tumor: IODnormal in TNM I, II, III, IV tumors was 1.43±0.34, 5.08±3.74, 4.99±1.08, 1.44±1.02, n = 42, P= 0.023] and serosa invasion (4.31±4.34 vs 2.00±2.03, P = 0.037). In poorly differentiated cancers (n = 33), the protein levels of ERK-1 and ERK-2 in stage III and IV tumors were higher than those in stage I and II tumors (2.64+3.01 vs 1.01±0.33, P= 0.022; 2.05±1.54 vs1.24±0.40, P= 0.030). Gastric cancer tissues with either lymph node involvement (2.49±2.91 vs1.03±0.36, P= 0.023; 1.98±1.49vs1.24±0.44, P= 0.036) or serosa invasion (2.39±2.82 vs 1.01±0.35, P= 0.022; 1.95±1.44 vs1.14±0.36, P=0.015) expressed higher protein levels of ERK-1 and ERK-2. In Borrmann II tumors, expression of ERK-2 and ERK-3 was increased compared with Borrmann III tumors (2.57±1.86 vs1.23±0.60, P= 0.022; 5.50±5.05 vs1.83±1.21, P= 0.014). Borrmann IV tumors expressed higher p38 protein levels. No statistically significant difference in expression of MAPKs was found when stratified to tumor size or histological grade (P>0.05). Protein levels of ERK-2, ERK-3 and MEK-1 in metastatic lymph nodes were 2-7 folds higher than those in adjacent normal mucosa. The immunohistochemistry demonstrated that ERK-1, ERK-2, ERK-3, p38 and MEK-1 proteins were mainly localized in cytoplasm. The expression of MEK-1 in gastric cancer cells metastasized to lymph nodes was higher than that of the primary site. CONCLUSION: MAPKs, particularly ERK subclass are overexpressed in the majority of gastric cancers. Overexpression of ERKs is correlated to TNM staging, serosa invasion, and lymph node involvement. The overexpression of p38 most likely plays a prominent role in certain morphological subtypes of gastric cancers. MEK-1 is also overexpressed in gastric cancer, particularly in metastatic lymph nodes. Upregulation of MARK signal transduction pathways may play an important role in tumorigenesis and metastatic potential of gastric cancer.

HBx activates FasL and mediates HepG2 cell apoptosis through MLK3-MKK7-JNKs signal module

AIM： To investigate the possible mechanism by which hepatitis B virus X protein （HBx） mediates apoptosis of HepG2 cells. METHODS： HBx expression vector pcDNA3.1-X was transfected into HepG2 cells to establish an HBx high- expression cellular model as pcDNA3.1-X transfected group. The pcDNA3.1-X and pSilencer3.1-shHBX （HBx antagonist） were cotransfected into HepG2 cells to es- tablish an HBx low-expression model as RNAi group. Untransfected HepG2 cells and HepG2 cells transfected with negative control plasmid were used as controls. Apoptosis rate, the expression of Fas/FasL signaling pathway-related proteins and the phosphorylation lev- els of MLK3, MKK7 and JNKs, which are upstream molecules of death receptor pathways and belong to the family of mitogen-activated protein kinases （MAPKs）,were measured in each group RESULTS： Compared with HepG2 cell group and RNAi group, apoptosis rate, the expression of Fas and FasL proteins, and the activation of MLK3, MKK7 and 3NKs were increased in the pcDNA3.1-X transfected group. The activation of JNKs and expression of FasL protein were inhibited in the pcDNA3.1-X transfected group when treated with a known JNK inhibitor, SP600125. When authors treated pcDNA3.1-X transfected group with K252a, a known MLK3 inhibitor, the activation of MLK3, MKK7 and 3NKs as well as expression of FasL protein was inhibited. Furthermore, cell apoptosis rate was also significantly declined in the presence of K252a in the pcDNA3.1-X transfected group. CONCLUSION： HBx can induce HepG2 cell apoptosis via a novel active MLK3-MKK7-JNKs signaling module to upregulate FasL protein expression.

Function and regulation of Aurora/Ipllp kinase family in cell division

During mitosis, the parent cell distributes its genetic materials equally into two daughter cells through chromosome segregation, a complex movements orchestrated by mitotic kinases and its effector proteins. Faithful chromosome segregation and cytokinesis ensure that each daughter cell receives a full copy of genetic materials of parent cell. Defects in these processes can lead to aneuploidy or polyploidy. Aurora/Ipl1p family, a class of conserved serine/threonine kinases, plays key roles in chromosome segregation and cytokinesis. This article highlights the function and regulation of Aurora/Ipllp family in mitosis and provides potential links between aberrant regulation of Aurora/Ipllp kinases and pathogenesis of human cancer.

Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis

Chromosome segregation in mitosis is orchestrated by the interaction of the kinetochore with spindle microtubules. Our recent study shows that NEK2A interacts with MAD 1 at the kinetochore and possibly functions as a novel integrator of spindle checkpoint signaling. However, it is unclear how NEK2A regulates kinetochore-microtubule attachment in mitosis. Here we show that NEK2A phosphorylates human Sgo 1 and such phosphorylation is essential for faithful chromosome congression in mitosis. NEK2A binds directly to HsSgol in vitro and co-distributes with HsSgol to the kinetochore of mitotic cells. Our in vitro phosphorylation experiment demonstrated that HsSgo 1 is a substrate of NEK2A and the phosphorylation sites were mapped to Ser^14 and Ser^507 as judged by the incorporation of 32^P. Although such phosphorylation is not required for assembly of HsSgo 1 to the kinetochore, expression of non-phosphorylatable mutant HsSgo 1 perturbed chromosome congression and resulted in a dramatic increase in microtubule attachment errors, including syntelic and monotelic attachments. These findings reveal a key role for the NEK2A-mediated phosphorylation ofHsSgo 1 in orchestrating dynamic kinetochore-microtubule interaction. We propose that NEK2A-mediated phosphorylation of human Sgo 1 provides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores.

Protective effects of non-mitogenic human acidic fibroblast growth factor on hydrogen peroxide-induced damage to cardiomyocytes in vitro

AIM： To study the protective effect of non-mitogenic human acidic fibroblast growth factor （FGF） on cardiac oxidative injury in vivo. METHODS： Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal SD mice and cultured in Dulbecco＇s minimum essential medium supplemented with 15% fetal bovine serum under an atmosphere of 50 mL/L CO2-95% air at 37℃, as well as assessed by immunooltochemical assay. We constructed the cardiomyoolte injury model by exposure to a certain concentration of H2O2. Cellular viability, superoxide dismutase （SOD） activity, leakage of maleic dialdehyde and anti-apoptosis effect were included to evaluate the cardiac protective effect of non-mitogenic human acidic FGF. RESULTS： Over 50% of the cardiomyocytes beat spontaneously on the 2nd d of culture and synchronously beat after being cultured for 3 d. Forty-eight hours after plating was completed, the purity of such cultures was 95% myocytes, assessed by an immunocytochemical assay. Cellular viability dramatically decreased with the increasing of the concentration of H2O2. Non-mitogenic human acidic FGF showed significant resistance to thetoxic effect of H2O2, significantly increased the cellular viability as well as the activity of SOD, and dramatically decreased the leakage of maleic dialdehyde as well as the cellular apoptosis rate. CONCLUSION： Hydrogen peroxide shows strong cytotoxicity to the cultured cardiac myocytes, and non-mitogenic human acidic FGF shows strong cardio-protective effect when exposed to a certain concentration of H2O2.

Inhibition of p38 mitogen-activated protein kinase may decrease intestinal epithelial cell apoptosis and improve intestinal epithelial barrier function after ischemia- reperf usion injury

AIM: To investigate the role of p38 mitogen-activated protein kinase in rat small intestine after ischemia-reperfusion (I/R)insult and the relationship between activation of p38 MAPK and apoptotic cell death of intestine.METHODS: Ninety Wistar rats were divided randomly into three groups, namely sham-operated group (C), I/R vehicle group (R) and SB203580 pre-treated group(S).In groups R and S, the superior mesenteric artery(SMA)was separated and occluded for 45 min, then released for reperfusion for0.25, 0.5, 1, 2, 6, 12 and 24 h. In group C, SMA was separated without occlusion. Plasma D-lactate levels were examined and histological changes were observed under a light microscope. The activity of p38 MAPK was determined by Western immunoblotting and apoptotic cells were detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUDP-biotin nick end labeling (TUNEL).RESULTS: Intestinal ischemia followed by reperfusion activated p38 MAPK, and the maximal level of activation (7.3-fold vs sham-operated group) was reached 30 min after I/R. Treatment with SB 203580, a p38 MAPK inhibitor,reduced intestinal apoptosis (26.72±3.39% vs62.50±3.08%in I/R vehicle, P＜0.01) and decreased plasma D-lactate level (0.78±0.15 mmol/L in I/R vehicle vs0.42±0.17 mmol/L in SB-treated group) and improved post-ischemic intestinal histological damage.CONCLUSION: p38 MAPK plays a crucial role in the signal transduction pathway mediating post-ischemic intestinal apoptosis, and inhibition of p38 MAPK may attenuate ischemia-reperfusion injury.

The effect of C-terminal fragment of JNK2 on the stability of p53 and cell proliferation

The basal activity of JNK is low in normal growing cells and inactivated JNK targets p53 for ubiquitination. To elucidate if the C-terminal part of JNK is responsible for its binding to p53, the low background tet-off inducible NIH3T3 cell line was selected by luciferase reporter gene and a double stable C-JNK Aa (203-424) cell line was established. After withdrawing tetracycline, the C-JNK fragment expression was induced and cell growth was dramati- cally inhibited 24 h later. However, the expresion of p53 was found to be increased after the induction of C-JNK fragment, evaluated by transfecting p21waf-luciferase reporter genes. Our further studies showed that C-JNK fragment could form complex with p53 both in vivo and in vitro. Induction of C-JNK fragment in vivo can increase p53 stability by inhibiting p53 ubiquitination.

Dynamic distribution of TTK in HeLa cells: insights from an ultrastructural study

Entry into mitosis is driven by signaling cascades of mitotic kinases.Our recent studies show that TTK,a kinetochore-associated protein kinase,interacts with CENP-E,a mitotic kinesin located to corona fiber ofkinetochore.Using immunoelectron microscopy,here we show that TTK is present at the nuclear pore adjacent complex of interphase HeLa cells.Upon nuclear envelope fragmentation,TTK targets to the outermostregion of the developing kinetochores ofmonoorient chromosome as well as to spindle poles.After stable attachment,throughout chromosome congression,TTK is a constituent of the corona fibers,extending up to 90 nm away from the kinetochore outer plate.Upon metaphase alignment,TTK departs from the kinetochore and migrates toward the centrosomes.Taken together,this evidence strongly supports a model in which TTK functions in spindle checkpoint signaling cascades at both kinetochore and centrosome.

Dynamic distribution of Ser-10 phosphorylated histone H3 in cytoplasm of MCF-7 and CHO cells during mitosis

The dynamic distribution of phosphorylated Histone H3 on Ser10 (phospho-H3) in cells was investigated to determineits function during mitosis. Human breast adenocarcinoma cells MCF-7, and Chinese hamster cells CHO were analyzedby indirect immunofluorescence staining with an antibody against phospho-H3. We found that the phosphorylationbegins at early prophase, and spreads throughout the chromosomes at late prophase. At metaphase, most of the phospho-H3 aggregates at the end of the condensed entity of chromosomes at equatorial plate. During anaphase and telophase,the fluorescent signal of phospho-H3 is detached from chromosomes into cytoplasm. At early anaphase, phospho-H3shows ladder bands between two sets of separated chromosome, and forms “sandwich-like structure” when the chro-mosomes condensed. With the cleavage progressing, the “ladders” of the histone contract into a bigger bright dot. Thenthe histone aggregates and some of compacted microtubules in the midbody region are composed into a “bar-like”complex to separate daughter cells. The daughter cells seal their plasma membrane along with the ends of the “bar”,inside which locates microtubules and modified histones, to finish the cytokinesis and keep the “bar complex” out of thecells. The specific distribution and kinetics of phospho-H3 in cytoplasm suggest that the modified histones may takepart in the formation of midbody and play a crucial role in cytokinesis.

Mitotic phosphorylation of PRC1 at Thr470 is required for PRC1 oligomerization and proper central spindle organization

During cell division, chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere. A dramatic remodeling of interpolar microtubules into an organized central spindle between the separating chromatids is required for the initiation and execution ofcytokinesis. Central spindle organization requires mitotic kinesins, the chromosomal passenger protein complex, and microtubule bundling protein PRC 1. PRC 1 is phosphorylated by Cdc2 at Thr470 and Thr481 during mitosis. However, the functional relevance of PRC 1 phosphorylation at Thr470 has remained elusive. Here we show that expression of the non-phosphorylatable mutant PRC 1T470A but not the phospho-mimicking mutant PRC 1^T470E causes aberrant organization of the central spindle. Immunoprecipitation experiment indicates that both PRC 1^T470A and PRC 1^T470E mutant proteins associate with wild-type PRC 1, suggesting that phosphorylation of Thr470 does not alter PRC 1 self-association. In addition, in vitro co-sedimentation experiment showed that PRC 1 binds to microtubule independent of the phosphorylation state of Thr470. Gel-filtration experiment suggested that phosphorylation of Thr470 promotes oligomerization of PRC 1. Given the fact that prevention of the Thr470 phosphorylation inhibits PRC 1 oligomerization in vitro and causes an aberrant organization of central spindle in vivo, we propose that this phosphorylation-dependent PRC 1 oligomerization ensures that central spindle assembly occurs at the appropriate time in the cell cycle.

Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation

Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine, a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems. In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.