The Bidirectional Effects of Arsenic on miRNA-21: A Systematic Review and Meta-analysis.

OBJECTIVE: Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanism by which miRNA-21 influences arsenic-induced cancer. METHODS: We used meta-analysis of published studies to determine how arsenic induces cancerous cells through miRNA-21. RESULTS: Low-dose arsenic exposure (⪕ 5 µmol/L) can increase miRNA-21 and phosphorylated signal transducter and activator of transcription 3 (pSTAT3) expression, and decrease programmed cell death protein 4 (PDCD4) and protein sprouty homolog 1 (Spry1) expression. High-dose arsenic exposure (> 5 µmol/L), can increase miRNA-21 expression, and decrease Spry1 and E-cadherin expression. Short-term arsenic exposure (⪕ 24 h) can increase miRNA-21 and pSTAT3 expression, and decrease PDCD4 expression. Moreover, long-term arsenic exposure (> 24 h) can increase the miRNA-21, STAT3, and pSTAT3 expression, and decrease PDCD4 expression. We found that activation of miRNA-21 and pSTAT3 were most pronounced following long-term arsenic exposure at low doses, and the effects on PDCD4 expression were most pronounced following short-term arsenic exposure at low doses. miRNA-21 inhibitors increased the expression of tumor suppressor genes PDCD4, PTEN, and Spry1 and miRNA-21-mimics suppressed the expression of these tumor suppressor genes. CONCLUSION: Arsenic can cause cancer by activating miRNA-21 and inhibiting the expression of PDCD4, PTEN, and Spry1.

Grape Seed Procyanidin Extract Reduces Arsenic-Induced Renal Inflammatory Injury in Male Mice.

The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.

Visceral Adiposity and Anthropometric Indicators as Screening Tools of Metabolic Syndrome among Low Income Rural Adults in Xinjiang.

Most previous studies on metabolic syndrome (MetS) examined urban and high income settings. We thus investigated the prevalence of MetS among a multi-ethnic population living in a low income rural area and explored the use of visceral adiposity and anthropometric indicators to identify men and women with MetS. We recruited 10,029 individuals of nomadic Kazakhs, rural Uyghur and Han residents in Xinjiang, China. MetS was defined by the Joint Interim Statement criteria. The receiver operating characteristic curve (ROC) was used to compare the area under the ROC curve (AUC) of each index. The age-adjusted prevalence of MetS was 21.8%. The visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI) and the waist-to-height ratio (WHtR) were significantly associated with MetS, independent of ethnic, age, and other covariates. The AUC of VAI, LAP and WHtR were all greater than 0.7, and the LAP was the index that most accurately identified MetS status in men (AUC = 0.853) and women (AUC = 0.817), with the optimal cut-offs of 34.7 and 27.3, respectively. In conclusion, the prevalence of MetS in low income rural adults of Xinjiang was high and the LAP was an effective indicator for the screening of MetS.

Interactions of Six SNPs in ABCA1gene and Obesity in Low HDL-C Disease in Kazakh of China.

OBJECTIVE: To detect the interactions between six functional polymorphisms in ABCA1 and obesity in Kazakhs with low HDL-C levels. METHODS: A total of 204 patients with low HDL-C and 207 health control subjects, which were randomly selected from among 5692 adult Kazakhs, were matched for age and sex. We genotyped ABCA1 single nucleotide polymorphisms of rs2515602, rs3890182, rs2275542, rs2230806, rs1800976, and rs4149313. RESULTS: (1) The genotypic and allelic frequencies of rs2515602, rs2230806 and rs4149313 were different between normal HDL-C and low HDL-C subjects, the genotypic frequency of rs2275542 was also different between normal HDL-C and low HDL-C subjects (p < 0.05); (2) the level of HDL-C (rs2515602 and rs2275542) in normal HDL-C subjects were different among the genotypes (p < 0.05); the levels of TC, LDL-C (rs2515602, rs4149313); TG (rs2515602, rs1800976, rs4149313) in low HDL-C patients were different among the genotypes (p < 0.05); (3) interactions between the rs3890182, rs2275542, rs180096, and rs4149313 polymorphisms in ABCA1 gene and obesity may be associated with low HDL-C disease; (4) the C-C-C-A-A-G, T-C-C-A-A-A, T-C-C-A-A-G, C-C-C-A-A-A, C-T-G-G-A-A, and T-T-C-G-A-A haplotypes were significant between the subjects with normal HDL-C and low HDL-C level (p < 0.05). CONCLUSIONS: The differences in serum lipid levels between normal HDL-C and low HDL-C subjects among Kazakhs might partly result from ABCA1 gene polymorphisms; ABCA1 gene polymorphisms may be associated with low HDL-C disease; the low HDL-C disease might partly result from interactions between ABCA1 gene polymorphisms and obesity; the C-C-C-A-A-G, T-C-C-A-A-A, and T-C-C-A-A-G haplotypes may serve as risk factors of low HDL-C disease among Kazakhs, the C-C-C-A-A-A, C-T-G-G-A-A, and T-T-C-G-A-A haplotypes may serve as protective factor of low HDL-C disease among Kazakhs.

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice.

OBJECTIVE: To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. METHODS: Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. RESULTS: ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. CONCLUSION: GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

Proliferation of small cell lung cancer cell line reduced by knocking-down PROX1 via shRNA in lentivirus.

The present study aimed to find whether PROX1 is expressed in small cell lung cancer (SCLC) cell lines, and whether PROX1 knockdown with shRNA via lentivirus resulted in decreased cell proliferation. SCLC cell lines H69, H82, H187 and H889 were selected for the study. PROX1 mRNA and protein levels were determined with real-time reverse-transcription polymerase chain reaction(RT-PCR) and western blot, respectively. The localization and distribution of PROX1 was mapped by immunocytochemistry with a specific antibody. Three pairs of shRNA were selected from a pool of shRNA pairs, and packaged into lentivirus particles to infect the above cell lines. The non-target sequence (NT) and a house-keeping gene, glyceraldehyde 3 phosphate dehydrogenase (GAPDH), were employed as controls. SCLC cell proliferation rates were measured with bromine deoxyuridine (BrdU) incorporation method. The results indicated levels of that PROX1 mRNA were detected in SCLC cell lines in the following rank order H69>H889>H187>H82. A similar profile for PROX1 protein expression was captured. The majority of PROX1 was concentrated at the cell nucleus. H69 was selected to represent the above SCLC cell lines. The PROX1 level in H69 cells was successfully reduced with shRNA lentivirus, and the cell proliferation rate of infected H69 cells was dramatically reduced by 20-50%. Hence, it is concluded that PROX1 expression in SCLC cell line is high, and can be reduced with shRNA lentivirus, thereby reducing the cell proliferation rate.

[Epidemiological study on overweight and obesity among rural adult residents in Hazakh and Uygur population in Xinjiang province, 2010].

OBJECTIVE: To investigate the prevalence and distribution features of overweight, obesity and abdominal obesity among rural adult residents in Hazakh and Uygur population in Xinjiang province, 2010. METHODS: Questionnaire-based survey and physical examination were conducted towards the 8611 subjects selected from Hazakh and Uygur residents aged over 18 years old in Yili Xinyuan County and Kashi Jiashi County in Xinjiang province by stratified cluster random sampling method; and thereby the results were analyzed and compared between the two ethnic populations. RESULTS: The prevalence of overweight in Hazakh(male: 29.5% (612/2078) and female: 26.4% (789/2991)) was higher than that in Uygur(male: 25.5% (440/1728) and female: 21.9% (397/1814)). The difference showed statistical significance (male: χ(2) = 7.50, female: χ(2) = 12.27, P < 0.01). The prevalence was higher in males than in females among the same ethic population (Hazakh: χ(2) = 5.79, Uygur: χ(2) = 6.28, P < 0.05). The prevalence of obesity in Hazakh(male:18.2% (379/2078) and female:18.1% (540/2991)) was higher than that in Uygur(male: 9.4% (163/1728) and female: 13.2% (240/1814)). The difference showed statistical significance (male: χ(2) = 59.90, female: χ(2) = 19.32, P < 0.01). The female prevalence was higher than male in Uygur (χ(2) = 12.66, P < 0.01); however, there was no statistically significant difference in the prevalence stratified by gender in Hazakh. The prevalence of abdominal obesity in Hazakh(male: 57.0% (1185/2078) and female: 60.2% (1801/2991)) was higher than that in Uygur(male: 46.9% (811/1728) and female: 59.5% (1080/1814)). The difference showed statistical significance (male: χ(2) = 38.54, P < 0.01; female: χ(2) = 0.216, P > 0.05). And the female prevalence was both higher than male in the two ethic populations (Hazakh: χ(2) = 5.15, P < 0.05; Uygur: χ(2) = 56.50, P < 0.01). CONCLUSION: The prevalence abdominal obesity among rural adult residents in Hazakh and Uygur population was much higher than the average level nationwide in China. Hazakh had a higher prevalence of overweight and obesity than Uygur.

[Epidemiological study on overweight and obesity among rural adult residents in Hazakh, Uygur and Han populations in Xinjiang].

OBJECTIVE: To investigate the prevalence and distribution of overweight, obesity and abdominal obesity among rural adult residents in Kazakh, Uygur and Han populations from Xinjiang and to provide the theory gist for prevention and cure on obesity in different ethnic groups. METHODS: Questionnaire-based survey and physical examination on 11 377 samples were conducted according to stratified cluster random samplings in Kazakh, Uygur and Han residents aged 18 years in Xinjiang. Prevalence rates on overweight, obesity and abdominal obesity between the three ethnic populations were analyzed and compared. RESULTS: The rates of overweight were 27.8%, 24.5% and 40.3% in kazakh, Uygur and Han populations, with the prevalence rates of obesity as 17.9%, 11.5% and 13.7%. However, the rates of abdominal obesity were 58.0%, 53.9% and 59.9%, respectively. The rates of overweight and abdominal obesity were the highest in Han population but the prevalence of obesity was the highest in Kazakh (P < 0.01). All the prevalence of overweight among the three ethnic populations and the rate of abdominal obesity in Han population were higher in males (P < 0.05) while the prevalence of obesity in the three ethnic populations and the rate of abdominal obesity in Uygur were diametrically opposite (P < 0.01). The prevalence rates of overweight, obesity and abdominal obesity all had an increasing trend in the three ethnic populations and the prevalence of abdominal obesity of all age groups was higher than the rates of overweight and obesity in the same age group. CONCLUSION: The prevalence rates of obesity and abdominal obesity in Kazakh and Uygur populations among rural adult residents were much higher in Xinjiang, so as the rate of overweight in the Hans. All the prevalence rates were different in ethnicities, age groups and sex. The prevalence rate of abdominal obesity was higher than the average data gathered from the nation.

[The epidemic situation of metabolic syndrome among the Uygur in Kashgar of Xinjiang in 2010].

OBJECTIVE: To analyze the prevalence and risk factors of metabolic syndrome (MS) in Xinjiang Uygur adults. METHODS: With cluster random sampling, investigations including questionnaire, physical examination and blood testing were performed among 3442 Uygur adults among in Kashgar of Xinjiang on November 2010. Prevalence of MS in groups with different characteristics were calculated and non-conditional logistic regression analysis were used to analyze the risk factors. RESULTS: The prevalence of MS was 21.2% (728/3442), and the age-adjusted prevalence was 18.5%. The prevalence among males and females was 14.5% (245/1694) (age-adjusted prevalence 12.7%) and 27.6% (483/1748) (age-adjusted prevalence 24.4%) respectively (P < 0.05). The prevalence of MS among 18 to 24 years old and 65 years old and above were 4.3% (21/490) and 28.9% (109/377) respectively. The prevalence of MS increased with age (χ(2) = 204.13, P < 0.05). The prevalence of low blood HDL-C, central obesity, hypertension, hypertriglyceridemia and hyperglycemia was 57.5% (1978/3442), 44.5% (1531/3442), 27.5% (948/3442), 20.2% (696/3442) and 8.6% (297/3442) respectively. Compared to age group 18 - 24, the risk of MS occurrence was higher in age group 25 - 34, 35 - 44, 45 - 54, 55 - 64 and 65 years-old above, the according OR (95%CI) values were 2.29 (1.38 - 3.81), 6.91 (4.31 - 11.09), 10.81 (6.72 - 17.40), 12.52 (7.74 - 20.26) and 10.20 (6.20 - 16.78), respectively. Smoking also increased the risk of MS (OR = 2.35, 95%CI: 1.64 - 3.37). CONCLUSION: The prevalence of MS in Xinjiang Uygur was in high level; The prevalence of MS is higher in female than in male; The risk factors of MS included female, age and smoking.

[Study on the prevalence of metabolic syndrome among the Kazakh population in Xinjiang].

OBJECTIVE: To analyze the prevalence of metabolic syndrome (MS) in Kazakh population, using the NCEP-ATPIII, CDS, IDF MS standards. METHODS: Questionnaire-based survey, physical examination and blood testing were conducted according to cluster random samplings in Kazakh residents in Xinjiang. 2745 samples were collected and diagnosed by NCEP-ATPIII, CDS, IDF standards to analyze the prevalence, with the distribution of its main components of MS, among the Kazakhs population. RESULTS: The prevalence rates of MS diagnosed by NCEP-ATPIII, CDS, IDF standards were 18.5%, 14.2% and 26.6%, while they became 14.2%, 10.9% and 20.1% after standardized by age. The prevalence of MS diagnosed by NCEP-ATPIII and IDF standard in males were higher than in females, while CDS was in the opposite situation. The prevalence of MS by these three standards increased with age. Among all the main components of MS diagnosed after these three standardization process, the prevalence of obesity, blood pressure rising and the abnormity of HDL-C were rather high. The prevalence of MS main components ≥ 1, ≥ 2, ≥ 3, ≥ 4, 5 ranked the highest compared to the lowest as to the IDF, ATPIII' and CDS diagnostic. standards CONCLUSION: The prevalence rates and gender distribution of MS diagnosed by different standards among Kazakhs were different. The prevalence of IDF standard was the highest, with the IDF standard better than the others in early identifying the risk factors of cardiovascular disease.

Prox1 Facilitates Transfected CHO Cell Proliferation through Activation of the AKT Signaling Pathway.

The homeobox transcription factor Prox1 plays an important role in the development of many embryonic organs. Previous studies indicated that Prox1 facilitates hepatic progenitor-cells proliferation. However, the underlying mechanism of Prox1 in tumor genesis, formation, and progression are poorly understood and need to be exploited. Herein, Chinese Hamster Ovary (CHO) cells were transfected and over-expressed human recombinant Prox1 gene, and developed several stable cell lines of Prox1-CHO after screening. The results indicated that over expression of Prox1 increased CHO cell proliferation in comparison to GFP-CHO and parental CHO cells, and Prox1 increased AKT phosphorylation and up-regulated PI3 Kinase expression. An AKT specific inhibitor-AKTi-X (5 µM) and a PI3 K inhibitor-LY294002 (5 µM) were able to reverse AKT phosphorylation and PI3 K expression induced by Prox1, respectively. Furthermore, AKTi-X but LY-294002 decreased Prox1-CHO cell proliferations at 48 and 72 h. Our results suggest that over expression of Prox1 facilitates CHO cell proliferation via activation of the AKT signaling pathway. This finding provides new insights into the mechanism of Prox1 mediated tumor growth and metastasis where Prox1 is rich.

[Relationship study of angiotensin II type 1 receptor gene A1166C polymorphism, food consumption and behavior on hypertension in Kazakh group, Xinjiang].

OBJECTIVE: To investigate the polymorphism of angiotensin II type 1 receptor (AT(1R)) gene A1166C and environmental factors on hypertension of Kazakh people. METHODS: Through the random program of SPSS 13.0, 220 cases were randomly selected from the confirmed hypertension patients, and 220 cases with normal blood pressure were selected as control group. All cases were investigated through the questionnaire and the related indexes were measured. By polymerase chain reaction (PCR) method, the genotypes were determined. RESULTS: (1) In hypertension group, the genotype frequency of AA and AC were 78.6% (173/220) and 21.4% (47/220), respectively, compared with control groups' 81.4% (179/220) and 18.6% (41/220), no significant difference was identified between these two groups (chi(2) = 0.537, P > 0.05). In hypertension group, the frequency of A and C allele were 89.0% and 11.0%, respectively, compared with 90.3% and 9.7% in control group. There was no significant difference between these two groups (chi(2) = 0.37, P > 0.05). (2) AC genotype might interact with excessive salt consumption (hypertension group, 31/220, 15.5%; control group 10/220, 4.5%, OR: 4.67, 95%CI: 2.15 - 10.15), overweight (hypertension group, 19/220, 8.6%; control group, 9/220, 4.1%, OR: 6.96, 95%CI: 2.33 - 20.76) and drinking large volume of salty milk (hypertension group, 20/220, 9.1%; control group, 10/220, 4.5%, OR: 2.67, 95%CI: 1.11 - 6.42) which will raise hypertension hazard of AC genotype. CONCLUSION: There is no relationship between the A1166C gene polymorphism of AT(1R) gene and hypertension of Kazakh people. AC genotypes might also interact with food consumption habit and behavior factors and increase the individual risk of hypertension.

[Study on anemia among premarital women in 6 counties from 1993 to 2003].

OBJECTIVE: To describe the prevalence of anemia and yearly trends (1993-2003) among women who came to the hospitals or maternal and child health units for premarital examinations in 6 counties of Jiangsu and Zhejiang provinces. METHODS: Data were obtained from the records of the premarital examinations in perinatal health care surveillance system that had been established since 1992 in these areas. We reviewed hemoglobin levels of those women who were enrolled in the perinatal health care surveillance system from 1993 to 2003. Anemia was defined according to the WHO (2001) criterion. We calculated the prevalence of anemia and analyzed the yearly trends based on the data of hemoglobin concentration. RESULTS: In the period of 1993-2003, there were 82 995 anemia cases identified among 193,434 women with an overall anemia rate as 42.9%. The rates of anemia were high (65.5%) in 1993 but low (25.8%) in 2003. 99.7% of the anemic women whose hemoglobin concentration were between 80-119.9 g/L. Time trend analysis indicated a significant decline on anemia rate while monthly analysis showed that the prevalence rates were high (48.2%) in September and low in March (39.5%). The results also showed that the prevalence rates of anemia were relatively higher in farmers and workers in rural enterprises, and lower in Han ethnicity than minorities. The higher prevalence rates of anemia were presented among the women with less education, lower body mass index, or at older age. CONCLUSION: For those premarital women in 6 counties of Jiangsu and Zhejiang provinces, the overall anemic rate presented a significant downward trend between 1993 and 2003 while the prevalence of anemia remained high, especially for the women with less education, lower body mass index or older ages.

Rottlerin induces calcium influx and protein degradation in cultured lenses independent of effects on protein kinase C delta.

Rottlerin has been widely accepted as a specific inhibitor of protein kinase C delta (PKC delta); however, recent data suggest that the specificity of this compound become a question. Herein, we address this issue using a lens organ culture system, as PKC delta might regulate the gap junction permeability in lens. Interestingly, we found that rottlerin induced the degradation of connexin50 more rapidly than that of PKC delta. Furthermore, comparison of rottlerin with a protonophore, carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP) that shares many characteristics with rottlerin, showed that both rottlerin and FCCP dramatically increased lens weight over time. This increase in lens weight was partially reversed by depletion of extracellular calcium with ethyleneglycoltetraacetic acid (EGTA) or by blocking L-type calcium channels with verapamil, suggesting rottlerin may induce calcium influx. Indeed, the rapid degradation of connexin50 (but not PKC delta) induced by rottlerin and FCCP was blocked by EGTA. In addition, rottlerin and FCCP also induced degradation of connexin46, filensin, vimentin and CP49. In order to determine whether this protein degradation is associated with the decrease of ATP due to uncoupling mitochondria by rottlerin, ATP content in lenses with different treatments were examined. The result indicated that EGTA had no effect on lens ATP content. Taken together, these data suggest that rottlerin, like FCCP, induces calcium influx, leading to protein degradation and cleavage in the lens, and that this effect is unrelated to the inhibition of PKC delta. Thus, extreme caution must be taken when considering use of rottlerin as a PKC delta inhibitor.

Glutamic acid reverses Pb2+-induced reductions of NMDA receptor subunits in vitro.

The objective of this study is to determine the effects of Pb2+ on N-methyl-d-aspartate receptor (NMDAR) subunits--NR1C1, NR2A and NR2B in primary cultured neuronal cells. We hypothesize that L-glutamic acid (GA) reverses Pb2+-induced NMDAR damage. Neuronal cells were isolated from the fetus brain at 18-20th day of gestation of pregnant Sprague Dawley (SD) rats. All experiments were included three independent cell preparations (N=3). The neuronal cells were exposed to Pb2+ (10(-10), 10(-9), 10(-8) and 10(-7)M) for 24 h. Neurons were pretreated with NMDAR agonist--L-glutamic acid (GA) (200 microM) and antagonists dizocipine (MK-801, 50 nM) for 1h and then exposed to 10(-7)M of Pb2+ for 24 h. Finally, GA at 2, 0.2 and 0.02 mM was incubated with neurons prior to Pb2+ exposure. Aliquots of NR1, NR2A and NR2B proteins from cell homogenate were immunoprecipitated with protein A agarose and detected by Western blotting. The addition of GA unconventionally reversed the reductions of NMDAR by Pb at protein levels, whereas MK-801 exacerbated Pb2+-induced damage. The protection by GA against Pb2+-induced reduction of NMDAR was dose-dependent. These findings suggest that the administration of GA may be a potential approach to intervene the Pb2+-induced NMDAR alterations.

PKC isoforms were reduced by lead in the developing rat brain.

A plethora of protein kinase C (PKC) isoforms play important roles in regulating synaptic plasticity and neurotransmitter release. Even though, most PKC isoforms are involved in Pb-induced neuronal toxicity, its mechanism is still unclear. The current study addresses the effect of Pb on PKC isoforms in different regions of the developing rat brain. Sprague-Dawley (SD) pregnant rats were exposed to 0.1% Pb as lead acetate dissolved in distilled deionized water (DDW) from gestation day 6 through 21 postnatal day (PND). Control rats were allowed to drink DDW. Pups were sacrificed on PND 1, 5, 10 and 45. Rat brain was immediately excised and separated into the brain stem (BS), the cerebellum (CB), the hippocampus (HC) and the frontal cortex (FC). The Pb level in different regions of the brain was determined using an analytical graphite tube atomizer (Varian). Typical PKC (alpha, beta, gamma), novel PKC (epsilon) and atypical PKC (mu) in the above brain regions were enriched by immunoprecipitation and later were assayed by Western blotting. The total, calcium-dependent and -independent PKC activities were determined by the radioactivity of total gamma-32P transferred to histone. The results indicated that on PND 1, Pb reduced the PKC-gamma protein in HC and FC, whereas on PND 5 the proteins of PKC isoforms (alpha, beta, gamma, epsilon, mu) in HC and FC were significantly reduced. These reductions in PKC proteins were higher in membrane fractions than in cytosolic fractions. On PND 10, Pb reduced all PKC isoforms. However, on PND 45, Pb had no significant effect on all PKC isoforms except epsilon. Pb inhibited the total PKC activity by 70% on PND 1 and 5, the bulk of these PKC activities were calcium-dependent. The results suggest that during early stages of the rat brain development, Pb exposure decreased PKC activities and also reduced PKC isoforms including PKC-gamma and epsilon which are reported to have roles in the memory formation and long-term potentiation (LTP).