Aim: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by an imbalance between tubular epithelial cell proliferation and apoptosis. We have previously shown that the mammalian target of rapamycin (mTOR) signalling pathway is aberrantly activated in the cystic kidneys of Han:SPRD rats with ADPKD. Because the Akt kinase is an upstream regulator of mTOR, we hypothesized that the activity of Akt could be enhanced in the kidneys of Han:SPRD rats.
Methods: Reverse transcription-polymerase chain reaction, western blot, enzyme-linked immunosorbent assay and immunohistochemistry were used to analyse Akt expression in rat polycystic kidneys.
Results: Wild-type (+/+) and heterozygous (Cy/+) Han:SPRD rats showed constitutive expression of Akt-1, -2 and -3 mRNA by reverse transcription-polymerase chain reaction analysis with no significant difference between Cy/+ and +/+ kidneys. Western blotting and enzyme-linked immunosorbent assay showed a significant increase in phosphorylated Akt in Cy/+ compared with +/+ kidneys. The pattern of immunoreactivity for phosphorylated Akt in kidney sections was the same in +/+ and in Cy/+ rats, with very low levels in interphase cells, but extremely bright signals in mitotic cells, beginning with the onset of the prophase. The in vivo incorporation of bromo-deoxyuridine revealed approximately a ninefold higher rate of proliferation in Cy/+ cyst epithelia compared with normal tubule epithelia in +/+ rats, while the expression of the cell cycle marker Ki67 revealed approximately a sixfold higher rate of proliferation. In summary, enhanced phosphorylation of Akt can be demonstrated in Cy/+ kidneys which correlates with a markedly elevated proliferation rate of epithelial cells in cysts. Mitotic but not resting cells display strong phosphorylation of Akt.
Conclusion: Because Akt is a proximal target of mTOR, its inhibition with specific antagonists could be useful to prevent or halt cystogenesis in ADPKD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1440-1797.2007.00811.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effects of pesticide dichlorvos on liver injury in rats and related toxicity mechanisms.
Ecotoxicol Environ Saf
January 2025
West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China. Electronic address:
Dichlorvos (DDVP) is an organophosphorus pesticide commonly utilized in agricultural production. Recent epidemiological studies suggest that exposure to DDVP correlates with an increased incidence of liver disease. However, data regarding the hepatotoxicity of DDVP remain limited.
View Article and Find Full Text PDFMitochondrial Mayhem: How cigarette smoke induces placental dysfunction through MMS19 degradation.
Ecotoxicol Environ Saf
January 2025
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, PR China. Electronic address:
Cigarette smoke (CS) has detrimental effects on placental growth and embryo development, but the underlying mechanisms remain unclear. This study aims to investigate the impact of CS on trophoblast cell proliferation and regulated cell death (RCD) by examining its interference with iron-sulfur cluster (ISC) proteins and the CIA pathway. Exposure to CS disrupted the cytosolic ISC assembly (CIA) pathway, downregulated ISC proteins, and decreased ISC maturation in the placenta of rats exposed to passive smoking.
View Article and Find Full Text PDFConformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.
Neurol Neuroimmunol Neuroinflamm
March 2025
Neuroimmunology Laboratory and Neuroimmunology Research Section, IRCCS Mondino Foundation, Pavia, Italy.
Background And Objectives: Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum.
View Article and Find Full Text PDFExploration and verification of the therapeutic mechanism of shenfu injection in sepsis-induced myocardial injury.
PLoS One
January 2025
Intensive Care Unit, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, PR China.
Background: Shenfu injection (SFI), derived from a traditional Chinese medicine (TCM) prescription, is an effective drug for the treatment of sepsis-induced myocardial injury (SIMI) with good efficacy, but its exact therapeutic mechanism remains unclear.
Methods: SwissTargetPrediction and GeneCards database were used to obtain relevant targets for SFI and SIMI. STRING 11.
Spontaneous oxycodone withdrawal disrupts sleep, diurnal, and electrophysiological dynamics in rats.
PLoS One
January 2025
Dept. of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, United States of America.
Opioid dependence is defined by an aversive withdrawal syndrome upon drug cessation that can motivate continued drug-taking, development of opioid use disorder, and precipitate relapse. An understudied but common opioid withdrawal symptom is disrupted sleep, reported as both insomnia and daytime sleepiness. Despite the prevalence and severity of sleep disturbances during opioid withdrawal, there is a gap in our understanding of their interactions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!