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Heme regulates protein homeostasis at transcription, protein translation, and degradation levels
Fang YANG, En-Duo WANG
Front Biol. 2010, 5 (6): 516-523.
https://doi.org/10.1007/s11515-010-7700-5
Heme, as a prosthetic group of proteins, is an iron-protoporphyrin involved in a wide range of cellular functions. Cellular heme levels vary due to the accurate balance of its synthesis and degradation. The “heme sensor protein” is currently a focus of investigation because heme has been found as a cellular signaling messenger involved in various biologic processes, including gene expression, protein localization, protein stability and microRNA processing. Several eukaryotic transcriptional factors can be regulated by heme, including heme activator protein (Hap1), Bach1, REV-erbα, and neuronal PAS domain protein 2 (NPAS2). Especially, the two circadian transcriptional factors serving as the heme sensor, REV-erbα and NPAS2, coordinate the circadian clock with metabolic pathways. It is well established that heme regulates the activity of heme-regulated eukaryotic initiation factor 2α (eIF2α) kinase (HRI), which serves as a feedback inhibitor of protein translation in both erythroid and non- erythroid cells. Additionally, heme is involved in protein degradation by inducing the degradation of several proteins such as the iron response regulator (Irr), iron regulatory protein 2 (IRP2), Bach1, and circadian factor period 2 (Per2). The N-end rule ubiquitin-dependent protein degradation pathway has also been identified as a sensor of heme, which blocks the function of arginyl-tRNA protein transferase (ATE1) and E3 ubiquitin ligase. In this review, we summarize the regulatory roles of heme at the levels of transcription, protein translation, and protein degradation, highlighting the role of heme in maintaining cellular homeostasis.
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Melatonin and mitochondria in aging
Weiguo DONG, Fang HUANG, Hongwen HE
Front Biol. 2010, 5 (6): 532-539.
https://doi.org/10.1007/s11515-010-0730-1
The worldwide prolongation of mean life expectancy has resulted in a rapid increase of the size of the elderly population, both in numbers and as a proportion of the whole. In addition, the incidence of age-related diseases is obviously increasing as the population ages. Finding means to preserve optimal health in old age has become a primary goal of biomedical research. Aging is a multifactorial process that includes progressive cellular loss, endocrine and metabolic deficits, reduced defense mechanisms and functional losses that increase the risk of death. Mitochondria fulfill a number of essential cellular functions and play a key role in the aging process. Melatonin, which is synthesized in the pineal gland and other organs, plays a role in the biologic regulation of aging. Noctural melatonin serum levels are high during childhood and diminish substantially as people age. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels; it also safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. In this article, we review the role of melatonin and mitochondria in aging.
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Behavioural responses of ex-situ captive hippopotamus (Hippopotamus amphibius) in lactation season: Maternal investment and plasticity of infant self-independence
Wei CHEN, Mallikarjun P. HANDIGUND, Jinghua MA, Lucia Lopez LOPEZ, Xianfu ZHANG
Front Biol. 2010, 5 (6): 556-563.
https://doi.org/10.1007/s11515-010-0540-5
In order to promote hippopotamus management in the captive and ex-situ environment, especially the control of behavioural and physiological status during breeding and lactation seasons, we conducted a preliminary study on behavioural responses of a pair of hippos including both mother and infant in Hangzhou Wildlife Park, China. The study of the captive hippos for about 1-month in the lactation season was carried out during August and September, 2009. The behavioural patterns were identified by all occurrence sampling and instantaneous scanning sampling methods with 5–10 min intervals. As a result, mother-offspring conflicts and interactions did occur throughout the whole study period. Early maternal investment showed a positive trend in activity rhythms (slope= 0.0014, Z = 0.3027, P<0.001) and a negative trend (slope= -0.0066, Z = 0.8807, P<0.001) in territorial occupation of water, all of which supported our hypotheses that the mother hippo might exert less care for the infant and cut down on her own obligations in nursing. For infant self-independence, during the whole lactation season, the primary trends of activities and territorial occupation dynamics of the infant hippo were slightly different from before, judging from linear models (slope= -0.0017, Z = 0. 3309, P<0.001). However, the frequencies of activities were not stable, especially at around 12 days of age. The trends of territorial occupation (slope= -0.0071, Z = 0. 904, P<0.001) also showed negative dynamics in water body occupation by the time the infant hippo grew up. The general trend (slope= -0.005, Z = 0.06, P<0.001) of suckling dynamics was demonstrably negative, with an upwards fluctuation at period 3 (10–15th day). This also illustrated that as the infant developed, the dependency on the mother was reduced at the end of the lactation season. In addition, a sharp decline between P3 and P4 also supported the mother-offspring conflict theory. In general, time budgets of hippos in active behaviour were (31.8±2.1)% for the mother and (32.1±2.6)% for the infant. Spatial distributions in water within temporal limitations were (80.1±2.7)% for the mother and (81.8±2.7)% for the infant. Behavioural dynamics showed strong synchronous relations between maternal investment and infant independence. Our current short-term investigation proves to be a key in management and conservation of hippopotami during the lactation season.
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