AIM: To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ (IGF-Ⅰ ) therapy (4 wk) is able to induce beneficial effects on damaged mitochondri...AIM: To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ (IGF-Ⅰ ) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS: Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Ⅰ treatment (2 μg/1O0 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three expedmental groups. RESULTS: Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF-Ⅰ therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Ⅰ and Ⅲ was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- Ⅰ therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION: These results show that IGF- Ⅰ exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.展开更多
OBJECTIVE To elucidate the molecular mechanism and the anti-breast cancer effect of polyphyllinⅠ,which is a natural compound extracted from Rhizoma of Paris polyphyllin.METHODS Human breast cancer cells were treated ...OBJECTIVE To elucidate the molecular mechanism and the anti-breast cancer effect of polyphyllinⅠ,which is a natural compound extracted from Rhizoma of Paris polyphyllin.METHODS Human breast cancer cells were treated with polyphyllinⅠ,after which DRP1-dependent mitochondrial fission and apoptosis,mitophagy and PINK1/PARK2 pathway were evaluated.A genetic approach was employed to determine how knockdown of PINK1 with sh RNA regulates polyphyllinⅠ-induced mitophagy and apoptosis.The inhibitory effect of polyphyllinⅠon tumor growth in a breast cancer cell xenograft mouse model was also examined.RESULTS PolyphyllinⅠenhanced the stabilization of full-length PINK1at the mitochondrial surface,leading to PARK2 recruitment to mitochondria,and culminating in mitophagy.PolyphyllinⅠalso induced dephosphorylation of DRP1 at Ser637 and mitochondrial translocation of DRP1,leading to mitochondrial fission and apoptosis.Knockdown of PINK1 evidently suppressed mitophagy stimulated by polyphyllinⅠ,and markedly enhanced DRP1-dependent mitochondrial fission and apoptosis induced by polyphyl inⅠ.Furthermore,suppression of DRP1 by mdivi-1 or sh RNA inhibits PINK1 knockdown-mediated mitochondrial fragmentation and apoptosis in response to polyphyllinⅠtreatment,suggesting that depletion of PINK1 lead to mitochondrial fragmentation due to excessive fission.Our in vivo study also showed that knockdown of PINK1potentiated polyphyllinⅠ-mediated inhibition of tumor growth in a breast cancer cell xenograft mouse model.CONCLUSION Our study provides a mechanism to support the role of PINK1 in the regulation of polyphyl inⅠ-induced mitophagy and apoptosis,and suggest polyphylinⅠas a potential drug for treatment of breast cancer.展开更多
[Object] This study was conducted to explore the genetic diversity and structure of the wild Repomucenus curvicornis inhabiting Liaoning Coast, China. [Method] The mitochondrial COⅠ gene and control region(CR) were...[Object] This study was conducted to explore the genetic diversity and structure of the wild Repomucenus curvicornis inhabiting Liaoning Coast, China. [Method] The mitochondrial COⅠ gene and control region(CR) were PCR amplified from the wild R. curvicornis populations from the Liaodong Bay(n=22) and the northern Yellow Sea(n=18), sequenced and analyzed for genetic diversity. [Result] The contents of A, T, C and G of 624 bp COⅠ gene were 24.09%, 31.04%, 25.28%, and 19.59%, and those of 460 bp CR fragment were 32.96%, 32.80%, 14.86% and 19.38%, respectively. The total number of variable sites, average number of nucleotide differences( k), haplotype diversity(H) and nucleotide diversity(π) based on COⅠ gene were 38, 4.67,(0.96±0.02) and(0.007 5±0.004 2), and those based on CR fragment were 26, 3.35,(0.97 ±0.02) and(0.007 3±0.004 3), respectively. Based on mitochondrial COⅠ gene and CR, the genetic diversity of Liaodong Bay population was lower than that of the northern Yellow Sea population. The AMOVA analysis based on CR fragments revealed almost significant genetic divergence between the Liaodong Bay and the northern Yellow Sea populations, while there was no significant genetic divergence based on COⅠ gene. The results showed that CR and COⅠ gene are effective molecular markers for detecting the genetic diversity of R. curvicornis population, while CR is more reliable than COⅠ gene in detecting the genetic structure. [Conclusion] CR is an appropriate marker for genetic analysis of marine fish population.展开更多
The aim of this study was to evaluate the genetic variability in bees Apis mellifera from Benin by using mitochondrial DNA (mtDNA) as a molecular marker in their cytochrome c oxidase subunit I and II (COI-COI1) in...The aim of this study was to evaluate the genetic variability in bees Apis mellifera from Benin by using mitochondrial DNA (mtDNA) as a molecular marker in their cytochrome c oxidase subunit I and II (COI-COI1) intergenic region. A total of 304 bee colonies were sampled in 27 municipalities of the cashew growing area of Benin. These samples were analyzed by the cleaved amplified polymorphisms technique for determining the haplotypes of subspecies present in the sampled population. Eight PCR-RFLP profiles of African lineage A were then identified in the 304 samples of bees investigated. Forty-nine percent (49%) of the samples showed the profile of haplotype A1 (subspecies adansonii of Zambia), 40% of haplotype A4 (subspecies scutellata of South Africa) and 3% of haplotype A 19 (subspecies adansonii of Guinea). Five other haplotypes of the African branch (A) that had been described in a previous study were also identified: new 1 (2%), new 2 (2%), new 3 (1%), new 4 (2%) and new 5 (1%). This study showed that A. rnellifera from Benin belonged only to lineage A with the predominance of haplotypes AI and A4. This study will contribute to the development of coherent policies for conservation of local bees in Benin.展开更多
采用PCR技术扩增6个地理种群桑天牛的线粒体细胞色素氧化酶Ⅰ(mt DNA COⅠ)基因序列,基于mt DNA COⅠ基因序列变异探讨不同地理分布桑天牛种群间的遗传距离、系统发育以及遗传分化程度。对6个地理种群的33个桑天牛样本的mt DNA COⅠ...采用PCR技术扩增6个地理种群桑天牛的线粒体细胞色素氧化酶Ⅰ(mt DNA COⅠ)基因序列,基于mt DNA COⅠ基因序列变异探讨不同地理分布桑天牛种群间的遗传距离、系统发育以及遗传分化程度。对6个地理种群的33个桑天牛样本的mt DNA COⅠ基因扩增产物的测序结果表明共有19个位点发生变异,占序列总长的4.0%,其中来自河南省济源的桑天牛有12个变异位点,来自浙江省的桑天牛有9个变异位点,来自河北省4个地区的桑天牛的变异位点较少;河北省的4个地理种群的遗传距离较小,在0.001 3-0.002 6之间,河北、河南、浙江种群间的遗传距离较大,其中河南种群与河北种群的遗传距离又远远大于浙江种群与河北种群的遗传距离,后2大地理种群分布区域的海拔更接近。利用MEGA4.1软件构建的NJ系统进化树显示,6个地理种群形成河北、河南和浙江3大地理分布格局;从遗传分化程度上来看,桑天牛种群的3大地理分布格局不存在共享的单元型,遗传分化系数(FST)在0.804 1-0.892 2范围内,遗传分化程度较高。综合分析认为,不同地理种群桑天牛存在分化的原因除地理分布外,更重要的是生态条件的差异。展开更多
基金Supported by The Spanish Program I + D, SAF 2005/08113
文摘AIM: To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ (IGF-Ⅰ ) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS: Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Ⅰ treatment (2 μg/1O0 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three expedmental groups. RESULTS: Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF-Ⅰ therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Ⅰ and Ⅲ was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- Ⅰ therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION: These results show that IGF- Ⅰ exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.
基金The project supported by National Natural Science Foundation of China(81402970,81402202,81402013,81202869)
文摘OBJECTIVE To elucidate the molecular mechanism and the anti-breast cancer effect of polyphyllinⅠ,which is a natural compound extracted from Rhizoma of Paris polyphyllin.METHODS Human breast cancer cells were treated with polyphyllinⅠ,after which DRP1-dependent mitochondrial fission and apoptosis,mitophagy and PINK1/PARK2 pathway were evaluated.A genetic approach was employed to determine how knockdown of PINK1 with sh RNA regulates polyphyllinⅠ-induced mitophagy and apoptosis.The inhibitory effect of polyphyllinⅠon tumor growth in a breast cancer cell xenograft mouse model was also examined.RESULTS PolyphyllinⅠenhanced the stabilization of full-length PINK1at the mitochondrial surface,leading to PARK2 recruitment to mitochondria,and culminating in mitophagy.PolyphyllinⅠalso induced dephosphorylation of DRP1 at Ser637 and mitochondrial translocation of DRP1,leading to mitochondrial fission and apoptosis.Knockdown of PINK1 evidently suppressed mitophagy stimulated by polyphyllinⅠ,and markedly enhanced DRP1-dependent mitochondrial fission and apoptosis induced by polyphyl inⅠ.Furthermore,suppression of DRP1 by mdivi-1 or sh RNA inhibits PINK1 knockdown-mediated mitochondrial fragmentation and apoptosis in response to polyphyllinⅠtreatment,suggesting that depletion of PINK1 lead to mitochondrial fragmentation due to excessive fission.Our in vivo study also showed that knockdown of PINK1potentiated polyphyllinⅠ-mediated inhibition of tumor growth in a breast cancer cell xenograft mouse model.CONCLUSION Our study provides a mechanism to support the role of PINK1 in the regulation of polyphyl inⅠ-induced mitophagy and apoptosis,and suggest polyphylinⅠas a potential drug for treatment of breast cancer.
基金Supported by the National Key R&D Program of China(2017YFC1404400)The National Natural Science Foundation of China(31770458)
文摘[Object] This study was conducted to explore the genetic diversity and structure of the wild Repomucenus curvicornis inhabiting Liaoning Coast, China. [Method] The mitochondrial COⅠ gene and control region(CR) were PCR amplified from the wild R. curvicornis populations from the Liaodong Bay(n=22) and the northern Yellow Sea(n=18), sequenced and analyzed for genetic diversity. [Result] The contents of A, T, C and G of 624 bp COⅠ gene were 24.09%, 31.04%, 25.28%, and 19.59%, and those of 460 bp CR fragment were 32.96%, 32.80%, 14.86% and 19.38%, respectively. The total number of variable sites, average number of nucleotide differences( k), haplotype diversity(H) and nucleotide diversity(π) based on COⅠ gene were 38, 4.67,(0.96±0.02) and(0.007 5±0.004 2), and those based on CR fragment were 26, 3.35,(0.97 ±0.02) and(0.007 3±0.004 3), respectively. Based on mitochondrial COⅠ gene and CR, the genetic diversity of Liaodong Bay population was lower than that of the northern Yellow Sea population. The AMOVA analysis based on CR fragments revealed almost significant genetic divergence between the Liaodong Bay and the northern Yellow Sea populations, while there was no significant genetic divergence based on COⅠ gene. The results showed that CR and COⅠ gene are effective molecular markers for detecting the genetic diversity of R. curvicornis population, while CR is more reliable than COⅠ gene in detecting the genetic structure. [Conclusion] CR is an appropriate marker for genetic analysis of marine fish population.
文摘The aim of this study was to evaluate the genetic variability in bees Apis mellifera from Benin by using mitochondrial DNA (mtDNA) as a molecular marker in their cytochrome c oxidase subunit I and II (COI-COI1) intergenic region. A total of 304 bee colonies were sampled in 27 municipalities of the cashew growing area of Benin. These samples were analyzed by the cleaved amplified polymorphisms technique for determining the haplotypes of subspecies present in the sampled population. Eight PCR-RFLP profiles of African lineage A were then identified in the 304 samples of bees investigated. Forty-nine percent (49%) of the samples showed the profile of haplotype A1 (subspecies adansonii of Zambia), 40% of haplotype A4 (subspecies scutellata of South Africa) and 3% of haplotype A 19 (subspecies adansonii of Guinea). Five other haplotypes of the African branch (A) that had been described in a previous study were also identified: new 1 (2%), new 2 (2%), new 3 (1%), new 4 (2%) and new 5 (1%). This study showed that A. rnellifera from Benin belonged only to lineage A with the predominance of haplotypes AI and A4. This study will contribute to the development of coherent policies for conservation of local bees in Benin.
文摘采用PCR技术扩增6个地理种群桑天牛的线粒体细胞色素氧化酶Ⅰ(mt DNA COⅠ)基因序列,基于mt DNA COⅠ基因序列变异探讨不同地理分布桑天牛种群间的遗传距离、系统发育以及遗传分化程度。对6个地理种群的33个桑天牛样本的mt DNA COⅠ基因扩增产物的测序结果表明共有19个位点发生变异,占序列总长的4.0%,其中来自河南省济源的桑天牛有12个变异位点,来自浙江省的桑天牛有9个变异位点,来自河北省4个地区的桑天牛的变异位点较少;河北省的4个地理种群的遗传距离较小,在0.001 3-0.002 6之间,河北、河南、浙江种群间的遗传距离较大,其中河南种群与河北种群的遗传距离又远远大于浙江种群与河北种群的遗传距离,后2大地理种群分布区域的海拔更接近。利用MEGA4.1软件构建的NJ系统进化树显示,6个地理种群形成河北、河南和浙江3大地理分布格局;从遗传分化程度上来看,桑天牛种群的3大地理分布格局不存在共享的单元型,遗传分化系数(FST)在0.804 1-0.892 2范围内,遗传分化程度较高。综合分析认为,不同地理种群桑天牛存在分化的原因除地理分布外,更重要的是生态条件的差异。