The ubiquitin specific protease 19 (USP19) regulates the hypoxia inducible factor 1a (HIF-1a) during hypoxia.
Journal - The Journal of biological chemistry
A proper cellular adaptation to low oxygen levels is essential for processes such as development, growth, metabolism and angiogenesis. The response to decrease in oxygen supply, referred to as hypoxia, is also involved in numerous human diseases including cancer, inflammatory conditions and vascular disease. The hypoxia inducible factor 1-a (HIF-1a), a key player in the hypoxic response, is kept under stringent regulation. At normoxia the levels are kept low as a consequence of the efficient degradation by the ubiquitin-proteasome system and in response to hypoxia the degradation is blocked and the accumulating HIF-1a promotes a transcriptional response essential for proper adaptation and survival. Here we show that the ubiquitin specific protease-19 (USP19) interacts with components of the hypoxia pathway including HIF-1a and rescues it from degradation independent of its catalytic activity. In the absence of USP19, cells fail to mount an appropriate response to hypoxia, indicating an important role for this enzyme in normal or pathological conditions.
Iron load and redox stress in skeletal muscle of aged rats.
Journal - Muscle & nerve (United States )
Loss of skeletal muscle mass (sarcopenia) is a major contributor to disability in old age. We used two-dimensional gel electrophoresis and mass spectrometry to screen for changes in proteins, and cDNA profiling to assess transcriptional regulations in the gastrocnemius muscle of adult (4 months) and aged (30 months) male Sprague-Dawley rats. Thirty-five proteins were differentially expressed in aged muscle. Proteins and mRNA transcripts involved in redox homeostasis and iron load were increased, representing novel components that were previously not associated with sarcopenia. Tissue iron levels were elevated in senescence, paralleling an increase in transferrin. Proteins involved in redox homeostasis showed a complex pattern of changes with increased SOD1 and decreased SOD2. These results suggest that an elevated iron load is a significant component of sarcopenia with the potential to be exploited clinically, and that mitochondria of aged striated muscle may be more vulnerable to radicals produced in cell respiration.
|ISSN : ||0148-639X|
|Mesh Heading : ||Age Factors Animals Electrophoresis, Gel, Two-Dimensional Gene Expression Profiling Gene Expression Regulation Iron Male Mass Spectrometry Muscle Proteins Muscle, Skeletal Oligonucleotide Array Sequence Analysis Oxidative Stress RNA, Messenger Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction methods methods physiology methods genetics metabolism methods biosynthesis methods|
|Mesh Heading Relevant : ||Aging metabolism metabolism physiology physiology|
Behavioral impairments of the aging rat.
Journal - Physiology & behavior (United States )
Several disturbances occurring during aging of humans and rodents alike stem from changes in sensory and motor functions. Using a battery of behavioral tests we have studied alterations in performance with advancing age in female and male rats of some frequently used strains. In parallel, we collected survival and body weight data. The median survival age was similar for female and male Sprague-Dawley rats, inbred female Lewis and outbred male Wistar rats (29-30 months). In contrast, male Fisher 344 had a significantly shorter median life span. During aging there is a gradual decline in locomotor activity and explorative behavior while disturbances of coordination and balance first became evident at more advanced age. In old age, also weight carrying capacity, limb movement and temperature threshold were impaired. While whole body weight continues to increase over the better part of a rats' life span, the behavioral changes in old age associated with a decrease in both total body weight and muscle mass. Dietary restriction increases median life span expectancy; retards the pace of behavioral aging and impedes sarcopenia. Housing in enriched environment did not improve the scoring in the behavioral tests but tended to increase median life span. Finally, there was an agreement between behavioral data collected from longitudinal age-cohorts and those obtained from multiple age-cohorts.
|ISSN : ||0031-9384|
|Mesh Heading : ||Age Factors Analysis of Variance Animals Behavior, Animal Behavioral Symptoms Exploratory Behavior Female Locomotion Male Motor Activity Pain Measurement Psychomotor Performance Rats Rats, Inbred F344 Rats, Sprague-Dawley Rats, Wistar Reaction Time Sex Factors Species Specificity physiology physiology physiology physiology|
|Mesh Heading Relevant : ||Aging physiology physiopathology|
Retrograde labeling of primary sensory neurons with fluorescent latex microspheres: a useful tool for long term tagging of neurons.
Journal - Journal of neuroscience methods (Netherlands )
In this study we have used fluorescent microspheres to retrogradely label primary sensory neurons in dorsal root ganglia (DRGs). Following injection into peripheral nerves, the animals were allowed to survive up to 480 days. Simple profile count indicates that there is a substantial retention of the labeling still after at least 480 days, i.e. about two-thirds of a rat's life span. Moreover, the appearance of the labeling remains quite distinct. Using established markers for axon damage of DRG neurons, we could detect a slight and transient effect of the peripheral nerve injection on the gene expression pattern. It is concluded that fluorescent microspheres represents an attractive means of tagging neurons in experiments covering long time periods.
|ISSN : ||0165-0270|
|Mesh Heading : ||Animals Axonal Transport Calcitonin Gene-Related Peptide Cell Count Female Fluorescein GAP-43 Protein Ganglia, Spinal Gene Expression Regulation Microspheres Nerve Degeneration Neuroanatomy Neurons, Afferent Neuropeptide Y Peripheral Nerves RNA, Messenger Rats Rats, Sprague-Dawley Time Factors physiology genetics diagnostic use genetics cytology metabolism drug effects physiology chemically induced metabolism physiopathology cytology metabolism genetics metabolism surgery metabolism|
|Mesh Heading Relevant : ||drug effects drug effects methods drug effects drug effects|