共查询到20条相似文献，搜索用时 15 毫秒
1.
Xiao‐Xi Pan Cheng‐Chao Ruan Xiu‐Ying Liu Ling‐Ran Kong Yu Ma Qi‐Hong Wu Hai‐Qing Li Yan‐Jun Sun An‐Qing Chen Qiang Zhao Fang Wu Xiu‐Jie Wang Ji‐Guang Wang Ding‐Liang Zhu Ping‐Jin Gao 《Aging cell》2019,18(4)
Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging‐related vascular diseases. Here, we take advantage of single‐cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging‐induced loss of peroxisome proliferator‐activated receptor‐γ coactivator‐1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery‐induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation. 相似文献
2.
Noha M. Shafik Rasha A. Gaber Darin A. Mohamed Abla M. Ebeid 《Journal of biochemical and molecular toxicology》2019,33(6)
Ulcerative colitis (UC) is a chronic gastrointestinal disorder interfering with life quality. A total of 60 male Wistar rats were divided into four equal groups: Control (group I), hesperidin only (group II), UC untreated (group III), and UC treated with hesperidin (group IV). Hesperidin had modulatory effects on UC pathogenesis, which might be through alleviating colonic sphingosine phosphate phosphatase 2 messenger RNA expression and sphingosine kinase‐1 levels, thus suppressing the subsequent downstream inflammatory and apoptotic cascades represented by decreased macrophage inflammatory protein‐1α and enhancement of B‐cell lymphoma 2 immunohistochemistry expression. Also, it improved mitochondrial biogenesis by increasing the peroxisome proliferator‐activated receptor‐gamma‐coactivator 1‐α level. It successfully restored redox potential as evidenced by marked alleviations of the nitric oxide and peroxynitrite levels, increasing total antioxidant capacity, and activating the superoxide dismutase enzyme. Also, hesperidin alleviated the UC disease activity index and improved the histopathological picture. These findings may offer a new therapeutic strategy for UC treatment. 相似文献
3.
4.
Nakamuta M Enjoji M Uchimura K Ohta S Sugimoto R Kotoh K Kato M Irie T Muta T Nawata H 《Cell biology international》2002,26(3):235-241
5.
Dan‐yan Zhu Jia‐ying Wu Huan Li Jie‐ping Yan Mei‐yuan Guo Yan‐bo Wo Yi‐jia Lou 《Journal of cellular biochemistry》2010,109(3):498-508
Relatively little is known about mitochondria metabolism in differentiating embryonic stem (ES) cells. Present research focused on several elements of cellular energy metabolism in hepatic‐like tissue derived from mouse ES cells. We demonstrated that mitochondrial location patterns and mitochondrial membrane potential (ΔΨm) existed in subsequent differentiation of the tissue. Mitochondriogenesis appeared at the early stage and kept a normal ΔΨm in differentiated mature hepatocytes. Peroxisome proliferator‐activated receptor‐α (PPAR‐α) expression was transitorily increased at the beginning, and kept a relatively low level later, which accompanied by expression of PPAR‐γ coactivator (PGC)‐1α, a master regulator of mitochondrial biogenesis. PPAR‐β expression showed robust up‐regulation in the late differentiation course. Enhanced co‐expressions of PPAR‐β and albumin with catalysis of UDP‐glucuronosyltransferases (UGTs) were observed at mature stage. While PPAR‐γ expression changed little before and after differentiation. Mitochondriogenesis could be accelerated by PPAR‐α specific agonist WY14643 and abolished by its antagonist GW6471 at the early stage. Neither of them affected mitochondrial ΔΨm and albumin generation in the differentiated hepatocytes. Furthermore, maturation of hepatic‐like tissue and mitochondriogenesis in hepatocyte could be efficiently stimulated by PPAR‐β specific agonist L165041 and abolished by PPAR‐β specific antagonist GSK0660, but not affected by PPAR‐γ specific agonist GW1929. In conclusion, the derived hepatic tissue morphologically possessed cellular energy metabolism features. PPAR‐α seemed only necessary for early mitochondriogenesis, while less important for ΔΨm retention in the mature tissue derived. The stimulation of PPAR‐β but not ‐γ enhanced hepatogenesis, hepatocytes maturation, and mitochondriogenesis. PPAR‐β took an important role in cellular energy metabolism of hepatogenesis. J. Cell. Biochem. 109: 498–508, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
6.
7.
Poorva Bhargava Vipin Kumar Verma Salma Malik Sana Irfan Khan Jagriti Bhatia Dharamvir Singh Arya 《Journal of biochemical and molecular toxicology》2019,33(5)
Hesperidin (HES), a flavanone glycoside, predominant in citrus fruits, has an agonistic activity on peroxisome proliferator‐activated receptor gamma (PPAR‐γ). PPAR‐γ is an inhibitor of cardiac hypertrophy (CH) signaling pathways. In this study, we investigated the cardioprotective effect of HES in isoproterenol (ISO)‐induced CH through PPAR‐γ agonistic activity. For this, male albino Wistar rats were divided into six groups (n = 6), that is, normal, ISO‐control, HES treatment group (200 mg kg?1; p.o.), HES per se (200 mg kg?1; p.o.), enalapril treatment group (30 mg kg?1; p.o.), and combination group (HES 200 mg kg?1; p.o.+enalapril 30 mg kg?1; p.o.). ISO (3 mg kg?1; s.c.) was administered to all groups except normal and per se to induce CH. HES or enalapril treatment of 28 days significantly attenuated pathological changes, improved cardiac hemodynamics, suppressed oxidative stress, and apoptosis along with an increased PPAR‐γ expression. The combination of enalapril with HES exhibited an effect similar to that of HES or enalapril alone on all the aforementioned parameters. Therefore, HES may be further evaluated as a promising molecule for the alleviation of CH. 相似文献
8.
Xiao‐Nv Wang Cong‐Cong Huang Yi‐Song Qian Xuan Huang Xiao‐Lei Wang Wan‐Zhu Jin Guang‐Ju Ji Mingui Fu Ke‐Yu Deng Hong‐Bo Xin 《Journal of cellular and molecular medicine》2018,22(1):101-110
It has been recently reported that CD38 was highly expressed in adipose tissues from obese people and CD38‐deficient mice were resistant to high‐fat diet (HFD)‐induced obesity. However, the role of CD38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD38 in adipogenesis and lipogenesis in vivo and in vitro, obesity models were generated with male CD38?/? and WT mice fed with HFD. The adipocyte differentiations were induced with MEFs from WT and CD38?/? mice, 3T3‐L1 and C3H10T1/2 cells in vitro. The lipid accumulations and the alternations of CD38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD‐fed mice or the MEFs, 3T3‐L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD38?/? male mice were significantly resistant to HFD‐induced obesity. CD38 expressions in adipocytes were significantly increased in WT mice fed with HFD, and the similar results were obtained from WT MEFs, 3T3‐L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPARγ, AP2 and C/EBPα were markedly attenuated in adipocytes from HFD‐fed CD38?/? mice and CD38?/? MEFs at late stage of adipocyte differentiation. Moreover, the expressions of SREBP1 and FASN were also significantly decreased in CD38?/? MEFs. Finally, the CD38 deficiency‐mediated activations of Sirt1 signalling were up‐regulated or down‐regulated by resveratrol and nicotinamide, respectively. These results suggest that CD38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/PPARγ‐FASN signalling pathway during the development of obesity. 相似文献
9.
10.
11.
12.
Juan Ji Teng‐Fei Xue Xu‐Dong Guo Jin Yang Ruo‐Bing Guo Juan Wang Ji‐Ye Huang Xiao‐Jie Zhao Xiu‐Lan Sun 《Aging cell》2018,17(4)
Microglia‐mediated neuroinflammation plays a dual role in various brain diseases due to distinct microglial phenotypes, including deleterious M1 and neuroprotective M2. There is growing evidence that the peroxisome proliferator‐activated receptor γ (PPARγ) agonist rosiglitazone prevents lipopolysaccharide (LPS)‐induced microglial activation. Here, we observed that antagonizing PPARγ promoted LPS‐stimulated changes in polarization from the M1 to the M2 phenotype in primary microglia. PPARγ antagonist T0070907 increased the expression of M2 markers, including CD206, IL‐4, IGF‐1, TGF‐β1, TGF‐β2, TGF‐β3, G‐CSF, and GM‐CSF, and reduced the expression of M1 markers, such as CD86, Cox‐2, iNOS, IL‐1β, IL‐6, TNF‐α, IFN‐γ, and CCL2, thereby inhibiting NFκB–IKKβ activation. Moreover, antagonizing PPARγ promoted microglial autophagy, as indicated by the downregulation of P62 and the upregulation of Beclin1, Atg5, and LC3‐II/LC3‐I, thereby enhancing the formation of autophagosomes and their degradation by lysosomes in microglia. Furthermore, we found that an increase in LKB1–STRAD–MO25 complex formation enhances autophagy. The LKB1 inhibitor radicicol or knocking down LKB1 prevented autophagy improvement and the M1‐to‐M2 phenotype shift by T0070907. Simultaneously, we found that knocking down PPARγ in BV2 microglial cells also activated LKB1–AMPK signaling and inhibited NFκB–IKKβ activation, which are similar to the effects of antagonizing PPARγ. Taken together, our findings demonstrate that antagonizing PPARγ promotes the M1‐to‐M2 phenotypic shift in LPS‐induced microglia, which might be due to improved autophagy via the activation of the LKB1–AMPK signaling pathway. 相似文献
13.
14.
15.
16.
Thomas M. Larsen Lesli H. Larsen Signe K. Torekov Jakob Ek Eva Black Sren Toubro Arne Astrup Thorkild I. A. Srensen Torben Hansen Oluf Pedersen 《Obesity (Silver Spring, Md.)》2005,13(6):953-958
Yet unidentified variants within the peroxisome proliferator‐activated receptor γ (PPARγ) 2 promoter may explain the inconsistent reports on associations between variants in the coding region and obesity or diabetes. Thus, we examined the putative PPARγ2 promoter (?3371 to +43 bp) for variants in 83 subjects with obesity or type 2 diabetes. We identified eight variants, seven of which were novel, including ?792A>G, ?816C>T, ?882T>C, ?1505G>A, ?1881C>T, ?1884T>A, ?2604T>C, and ?2953A>G. The variants ?816C>T, ?1505G>A, ?1881C>T, and ?2604T>C were in total linkage disequilibrium, and there was a high degree of linkage disequilibrium between several of the novel variants and Pro12Ala. The novel variants were, together with Pro12Ala and 1431C>T, examined for relationships with obesity among 234 men with early‐onset obesity with a BMI at age ～20 years of 33.2 ± 2.5 kg/m2 and 323 nonobese men with a BMI of 21.7 ± 2.5 kg/m2, who were also reexamined after ～29 years. The prevalence of the identified variants was not significantly different between the two groups, and the variants did not affect changes in BMI over time. In conclusion, the identified novel variants in the PPARγ2 promoter region do not explain the reported discrepancies in the association of previously identified variants with obesity and type 2 diabetes. 相似文献
17.
Xue Xue Weiwei Zhang Jifeng Zhu Xiaojun Chen Sha Zhou Zhipeng Xu Gang Hu Chuan Su 《Journal of cellular and molecular medicine》2019,23(4):2568-2582
Aquaporin‐4 (AQP4), the main water‐selective membrane transport protein in the brain, is localized to the astrocyte plasma membrane. Following the establishment of a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced Parkinson's disease (PD) model, AQP4‐deficient (AQP4?/?) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH+)‐positive neurons than did wild‐type AQP4 (AQP4+/+) controls. Microglia are the most important immune cells that mediate immune inflammation in PD. However, recently, few studies have reported why AQP4 deficiency results in more severe hypermicrogliosis and neuronal damage after MPTP treatment. In this study, transforming growth factor‐β1 (TGF‐β1), a key suppressive cytokine in PD onset and development, failed to increase in the midbrain and peripheral blood of AQP4?/? mice after MPTP treatment. Furthermore, the lower level of TGF‐β1 in AQP4?/? mice partially resulted from impairment of its generation by astrocytes; reduced TGF‐β1 may partially contribute to the uncontrolled microglial inflammatory responses and subsequent severe loss of TH+ neurons in AQP4?/? mice after MPTP treatment. Our study provides not only a better understanding of both aetiological and pathogenical factors implicated in the neurodegenerative mechanism of PD but also a possible approach to developing new treatments for PD via intervention in AQP4‐mediated immune regulation. 相似文献
18.
19.
Antonio Luchicchi Salvatore Lecca Stefano Carta Giuliano Pillolla Anna L. Muntoni Sevil Yasar Steven R. Goldberg Marco Pistis 《Addiction biology》2010,15(3):277-288
The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme that degrades the endogenous cannabinoid N‐acylethanolamine (NAE) anandamide and the endogenous non‐cannabinoid NAEs oleoylethanolamide and palmitoylethanolamide, blocks nicotine‐induced excitation of ventral tegmental area (VTA) dopamine (DA) neurons and DA release in the shell of the nucleus accumbens (ShNAc), as well as nicotine‐induced drug self‐administration, conditioned place preference and relapse in rats. Here, we studied whether effects of FAAH inhibition on nicotine‐induced changes in activity of VTA DA neurons were specific for nicotine or extended to two drugs of abuse acting through different mechanisms, cocaine and morphine. We also evaluated whether FAAH inhibition affects nicotine‐, cocaine‐ or morphine‐induced actions in the ShNAc. Experiments involved single‐unit electrophysiological recordings from DA neurons in the VTA and medium spiny neurons in the ShNAc in anesthetized rats. We found that URB597 blocked effects of nicotine and cocaine in the ShNAc through activation of both surface cannabinoid CB1‐receptors and alpha‐type peroxisome proliferator‐activated nuclear receptor. URB597 did not alter the effects of either cocaine or morphine on VTA DA neurons. These results show that the blockade of nicotine‐induced excitation of VTA DA neurons, which we previously described, is selective for nicotine and indicate novel mechanisms recruited to regulate the effects of addicting drugs within the ShNAc of the brain reward system. 相似文献
20.
Jun Li Wenbo Ke Qi Zhou Yongzhong Wu Hong Luo Hong Zhou Bin Yang Yu Guo Qichang Zheng Yong Zhang 《Journal of cellular and molecular medicine》2014,18(9):1863-1873
Tumour necrosis factor (TNF)‐α has been considered to induce ischaemia‐reperfusion injury (IRI) of liver which is characterized by energy dysmetabolism. Peroxisome proliferator–activated receptor‐γ co‐activator (PGC)‐1α and mitofusion2 (Mfn2) are reported to be involved in the regulation of mitochondrial function. However, whether PGC‐1α and Mfn2 form a pathway that mediates liver IRI, and if so, what the underlying involvement is in that pathway remain unclear. In this study, L02 cells administered recombinant human TNF‐α had increased TNF‐α levels and resulted in down‐regulation of PGC‐1α and Mfn2 in a rat liver IRI model. This was associated with hepatic mitochondrial swelling, decreased adenosine triphosphate (ATP) production, and increased levels of reactive oxygen species (ROS) and alanine aminotransferase (ALT) activity as well as cell apoptosis. Inhibition of TNF‐α by neutralizing antibody reversed PGC‐1α and Mfn2 expression, and decreased hepatic injury and cell apoptosis both in cell culture and in animals. Treatment by rosiglitazone sustained PGC‐1α and Mfn2 expression both in IR livers, and L02 cells treated with TNF‐α as indicated by increased hepatic mitochondrial integrity and ATP production, reduced ROS and ALT activity as well as decreased cell apoptosis. Overexpression of Mfn2 by lentiviral‐Mfn2 transfection decreased hepatic injury in IR livers and L02 cells treated with TNF‐α. However, there was no up‐regulation of PGC‐1α. These findings suggest that PGC‐1α and Mfn2 constitute a regulatory pathway, and play a critical role in TNF‐α‐induced hepatic IRI. Inhibition of the TNF‐α or PGC‐1α/Mfn2 pathways may represent novel therapeutic interventions for hepatic IRI. 相似文献