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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 6. |
- Alavian, S.M., et al.
(författare)
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Virus-triggered autophagy in viral hepatitis - possible novel strategies for drug development
- 2011
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Ingår i: Journal of Viral Hepatitis. - : Blackwell Publishing. - 1352-0504 .- 1365-2893. ; 18:12, s. 821-830
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Forskningsöversikt (refereegranskat)abstract
- . Autophagy is a very tightly regulated process that is important in many cellular processes including development, differentiation, survival and homoeostasis. The importance of this process has already been proven in numerous common diseases such as cancer and neurodegenerative disorders. Emerging data indicate that autophagy plays an important role in some liver diseases including liver injury induced by ischaemia reperfusion and alpha-1 antitrypsin Z allele-dependent liver disease. Autophagy may also occur in viral infection, and it may play a crucial role in antimicrobial host defence against pathogens, while supporting cellular homoeostasis processes. Here, the latest findings on the role of autophagy in viral hepatitis B and C infection, which are both serious health threats, will be reviewed.
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| 7. |
- Bollano, Entela, 1970, et al.
(författare)
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Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene.
- 2000
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Ingår i: Endocrinology. - 0013-7227. ; 141:6, s. 2229-35
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.
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| 8. |
- Cedernaes, Jonathan, et al.
(författare)
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A single night of partial sleep loss impairs fasting insulin sensitivity but does not affect cephalic phase insulin release in young men
- 2016
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 25:1, s. 5-10
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Tidskriftsartikel (refereegranskat)abstract
- The present study sought to investigate whether a single night of partial sleep deprivation (PSD) would alter fasting insulin sensitivity and cephalic phase insulin release (CPIR) in humans. A rise in circulating insulin in response to food-related sensory stimulation may prepare tissues to break down ingested glucose, e.g. by stimulating rate-limiting glycolytic enzymes. In addition, given insulin's anorexigenic properties once it reaches the brain, the CPIR may serve as an early peripheral satiety signal. Against this background, in the present study 16 men participated in two separate sessions: one night of PSD (4.25 h sleep) versus one night of full sleep (8.5 h sleep). In the morning following each sleep condition, subjects' oral cavities were rinsed with a 1-molar sucrose solution for 45 s, preceded and followed by blood sampling for repeated determination of plasma glucose and serum insulin concentrations (-3, +3, +5, +7, +10 and +20 min). Our main result was that PSD, compared with full sleep, was associated with significantly higher peripheral insulin resistance, as indicated by a higher fasting homeostasis model assessment of insulin resistance index (+16%, P = 0.025). In contrast, no CPIR was observed in any of the two sleep conditions. Our findings indicate that a single night of PSD is already sufficient to impair fasting insulin sensitivity in healthy men. In contrast, brief oral cavity rinsing with sucrose solution did not change serum insulin concentrations, suggesting that a blunted CPIR is an unlikely mechanism through which acute sleep loss causes metabolic perturbations during morning hours in humans.
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| 9. |
- Cedernaes, Jonathan, et al.
(författare)
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Learning and sleep-dependent consolidation of spatial and procedural memories are unaltered in young men under a fixed short sleep schedule
- 2016
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Ingår i: Neurobiology of Learning and Memory. - : Elsevier BV. - 1074-7427 .- 1095-9564. ; 131, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate if a fixed short sleep schedule impairs one of the main functions of sleep, which is to consolidate newly learned memories. Methods: Sixteen young men participated in two experimental conditions, each of which lasted for 3 consecutive days and nights in our laboratory: a short sleep schedule (4.25-h sleep opportunity per night) versus a normal sleep schedule (8.5 h per night). In the evening after two experimental nights, participants learned locations of 15 card pairs (spatial memory task) and a procedural finger tapping sequence task. Post-sleep retrieval of both memory tasks was tested the next morning. Results: The short sleep schedule, compared with the normal sleep schedule, considerably altered sleep characteristics, e.g. the proportion of time in slow-wave sleep increased across the three experimental nights. In contrast, neither learning in the evening of day 2, nor subsequent overnight memory consolidation (i.e. concerning the change in memory performance between pre-sleep learning on day 2 and post sleep retrieval on day 3) differed between the normal and short sleep schedule conditions. Conclusions: Our findings suggest that learning in the evening and subsequent sleep-dependent consolidation of procedural and spatial memories are unaltered in young men living under a fixed short sleep schedule. Future studies are warranted to validate our findings in other groups (e.g. adolescents and older subjects) and after more prolonged chronic sleep loss paradigms.
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| 10. |
- Cedernaes, Jonathan, et al.
(författare)
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Short Sleep Makes Declarative Memories Vulnerable to Stress in Humans
- 2015
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 38:12, s. 1861-1868
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Tidskriftsartikel (refereegranskat)abstract
- Study Objective: This study sought to investigate the role of nocturnal sleep duration for the retrieval of oversleep consolidated memories, both prior to and after being cognitively stressed for similar to 30 minutes the next morning. Design: Participants learned object locations (declarative memory task comprising 15 card pairs) and a finger tapping sequence (procedural memory task comprising 5 digits) in the evening. After learning, participants either had a sleep opportunity of 8 hours (between similar to 23:00 and similar to 07:00, full sleep condition) or they could sleep between similar to 03:00 and similar to 07:00 (short sleep condition). Retrieval of both memory tasks was tested in the morning after each sleep condition, both before (similar to 08:30) and after being stressed (similar to 09:50). Setting: Sleep laboratory. Participants: 15 healthy young men. Results: The analyses demonstrated that oversleep memory changes did not differ between sleep conditions. However, in their short sleep condition, following stress hallmarked by increased subjective stress feelings, the men were unable to maintain their pre-stress performance on the declarative memory task, whereas their performance on the procedural memory task remained unchanged. While men felt comparably subjectively stressed by the stress intervention, overall no differences between pre- and post-stress recalls were observed following a full night of sleep. Conclusions: The findings suggest that 8-h sleep duration, within the range recommended by the US National Sleep Foundation, may not only help consolidate newly learned procedural and declarative memories, but also ensure full access to both during periods of subjective stress.
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