Actin-binding protein IPP (Intracisternal A particle-promoted polypeptide) (IPP) (Kelch-like protein 27) [KLHL27]

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Toxic effect of the novel chiral insecticide IPP and its biodegradation intermediate in nematode Caenorhabditis elegans.

Caenorhabditis elegans, a kind of model organism, was used to investigate biodegradation pathway of IPP and M1 in nematodes, in vivo toxicity from IPP and M1 and the possible underlying molecular mechanism. The results showed that both IPP and M1 could decrease lifespan, locomotion behavior, reproductive ability and AChE activity. During IPP biodegradation process, three intermediates (M1-M3) were monitored and identified. Based on the identified metabolites and their biodegradation courses, a possible biodegradation pathway was proposed. IPP was probably transformed to different three metabolites in nematodes through oxidation and elimination of methyl and propyl etc. Under the same concentration, IPP had more severe toxicity than M1 on nematodes. IPP and M1 might reduce lifespan and decrease reproductive ability through influencing insulin/IGF signaling pathway and TOR signaling pathway. They could decrease expression levels of daf-16, sgk-1, aak-2, daf-15 and rict-1 genes, which involved in IGF and TOR signaling pathway.

MeSH Terms

  • Acetylcholinesterase
  • Animals
  • Azabicyclo Compounds
  • Biodegradation, Environmental
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Gene Expression Regulation
  • Indoles
  • Insecticides
  • Longevity
  • Pyridines
  • Reproduction
  • Signal Transduction
  • Somatomedins

Keywords

  • Biodegradation intermediate
  • Caenorhabditis elegans
  • Nematode
  • Paichongding
  • Toxic effect


The inositol pyrophosphate pathway in health and diseases.

Inositol pyrophosphates (IPPs) are present in organisms ranging from plants, slime moulds and fungi to mammals. Distinct classes of kinases generate different forms of energetic diphosphate-containing IPPs from inositol phosphates (IPs). Conversely, polyphosphate phosphohydrolase enzymes dephosphorylate IPPs to regenerate the respective IPs. IPPs and/or their metabolizing enzymes regulate various cell biological processes by modulating many proteins via diverse mechanisms. In the last decade, extensive research has been conducted in mammalian systems, particularly in knockout mouse models of relevant enzymes. Results obtained from these studies suggest impacts of the IPP pathway on organ development, especially of brain and testis. Conversely, deletion of specific enzymes in the pathway protects mice from various diseases such as diet-induced obesity (DIO), type-2 diabetes (T2D), fatty liver, bacterial infection, thromboembolism, cancer metastasis and aging. Furthermore, pharmacological inhibition of the same class of enzymes in mice validates the therapeutic importance of this pathway in cardio-metabolic diseases. This review critically analyses these findings and summarizes the significance of the IPP pathway in mammalian health and diseases. It also evaluates benefits and risks of targeting this pathway in disease therapies. Finally, future directions of mammalian IPP research are discussed.

MeSH Terms

  • Animals
  • Carbohydrate Conformation
  • Inositol Phosphates
  • Mammals
  • Metabolic Networks and Pathways

Keywords

  • DIPP
  • IP6K
  • PPIP5K
  • TNP
  • aging
  • cancer
  • cardiovascular disease
  • development
  • diabetes
  • inositol pyrophosphate
  • obesity


Integrin-linked kinase: A new actor in the ageing process?

Integrin-linked kinase (ILK) is a protein located in focal adhesion complexes that is linked to the cytoplasmic domain of integrin receptors. Together with PINCH and parvin, ILK forms the IPP complex, which is associated with conserved intracellular signalling pathways and integrin regulation of the actin cytoskeleton. ILK plays an essential role in a wide variety of cellular functions, including cell migration, differentiation, survival, and division. The present review summarizes recent evidence, suggesting a new role for ILK in organismal ageing and cellular senescence, indicating that ILK is a key regulator of longevity and premature cellular senescence induced by extracellular stressors.

MeSH Terms

  • Aging
  • Animals
  • Cell Adhesion
  • Cell Differentiation
  • Cell Movement
  • Cellular Senescence
  • Humans
  • Protein-Serine-Threonine Kinases
  • Signal Transduction

Keywords

  • Extracellular matrix
  • Longevity
  • Senescence


Efficacy of a computer-based cognitive training program in older people with subjective memory complaints: a randomized study.

the aim of this study was to investigate the effect of computer-assisted cognitive training in healthy older adults with subjective memory complaints. Forty older adults, mean age (standard deviation) = 66.4 (5.6) with subjective memory complaints, were included in this study. Participants were randomly assigned to an integrated psychostimulation program (IPP) (N = 17), a computerized cognitive training (CCT) (N = 12) or a control group (N = 11). The training was applied for 8 weeks (90 min/d, 4 d/week for IPP, and 60 min/d, 4 d/week for CCT). Effectiveness was evaluated with a neuropsychological assessment battery, used before and after the implementation of the cognitive training. According to the data analysis, with analysis of covariance (ANCOVA), we found a statistically significant change in the majority of the cognitive variables measured before and after the experimental conditions compared with the control group. Although, according to a paired t-test, the IPP was more effective in the improvement of cognitive functioning in the participants. Additionally, a decrease in anxiety symptoms was observed after the cognitive intervention in IPP and CCT conditions. Our findings suggested that cognitive training of moderate intensity, supported by a web platform, could lead to significant improvements in cognitive and psychological well-being in older people with subjective memory complaints.

MeSH Terms

  • Aged
  • Aging
  • Cognitive Remediation
  • Female
  • Humans
  • Male
  • Memory Disorders
  • Middle Aged
  • Outcome Assessment, Health Care
  • Therapy, Computer-Assisted

Keywords

  • Memory
  • computerized cognitive training
  • psychology of aging
  • successful aging