Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Prolonged ischaemia and reperfusion in heart transplantation results in mitochondrial dysfunction and loss of cardio-energetics. Improved myocardial tolerance to ischaemia-reperfusion can be increased by de novo synthesis of heat shock protein (Hsp) groups, transiently expressed following mild hyperthermic or oxidative stress. Consideration of the roles of various Hsp in ischaemic-reperfused myocardium can provide new insights into potential therapeutic adjuncts to cardiac surgery. 2. Several Hsp classes have been located within or in association with mitochondrial elements. Cardiac Hsp research has focused primarily on the 70 kDa group, involved in protein folding functions within the cytosol and matrix. Similarly, Hsp 60 and 10 have been shown to form a mitochondrial chaperonin complex conferring protection to ischaemia-challenged myocytes. Equally pertinent is Hsp 32, an isoform of the haem-metabolizing enzyme heme oxygenase. 3. Our studies have shown that mitochondrial respiratory enzyme activity can be protected by Hsp, affording protection to cardiac energetics during preservation for transplantation. Upregulation of Hsp 32, 60 and 72 in rats, achieved by mild hyperthermic stress, improved cardiac function, ultrastructure and mitochondrial respiratory and complex activities in ex vivo perfused hearts subjected to cold cardioplegic arrest and ischaemia-reperfusion. Pre-ischaemic mitochondrial complex activities were increased in heat stress versus sham-treated groups for complex I, IV and V. 4. Investigation of the direct effect of upregulation of Hsp 72 by gene transfection resulted in a similar pattern of response, with increased complex I activity and improved ventricular function. 5. These studies provide the first evidence of Hsp-mediated enhancement of mitochondrial energetic capacity. Enhanced protection of mitochondrial energetics, as a result of increased Hsp expression, contributes to the recovery of myocardial function in ischaemia-reperfusion.
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PMID:Cardiac mitochondrial complex activity is enhanced by heat shock proteins. 1254 63

Sensory epithelia of the inner ear contain mechanosensory hair cells (HCs) and glia-like supporting cells (SCs), both of which are required for hearing and balance functions. Each of these cell types has unique responses to ototoxic and cytoprotective stimuli. Non-lethal heat stress in the mammalian utricle induces heat shock proteins (HSPs) and protects against ototoxic drug-induced hair cell death. Induction of HSPs in the utricle demonstrates cell-type specificity at the protein level, with HSP70 induction occurring primarily in SCs, while HSP32 (also known as heme oxygenase 1, HMOX1) is induced primarily in resident macrophages. Neither of these HSPs are robustly induced in HCs, suggesting that HCs may have little capacity for induction of stress-induced protective responses. To determine the transcriptional responses to heat shock of these different cell types, we performed cell-type-specific transcriptional profiling using the RiboTag method, which allows for immunoprecipitation (IP) of actively translating mRNAs from specific cell types. RNA-Seq differential gene expression analyses demonstrated that the RiboTag method identified known cell type-specific markers as well as new markers for HCs and SCs. Gene expression differences suggest that HCs and SCs exhibit differential transcriptional heat shock responses. The chaperonin family member Cct8 was significantly enriched only in heat-shocked HCs, while Hspa1l (HSP70 family), and Hspb1 and Cryab (HSP27 and HSP20 families, respectively) were enriched only in SCs. Together our data indicate that HCs exhibit a limited but unique heat shock response, and SCs exhibit a broader and more robust transcriptional response to protective heat stress.
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PMID:Cell-Specific Transcriptional Responses to Heat Shock in the Mouse Utricle Epithelium. 3252 49