Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HSP27 and MKBP translocate from the cytosolic to myofibril fraction in ischemic rat heart as demonstrated by immunoblotting. Immunohistochemistry analysis showed that ischemia enhances the Z line labeling of HSP27 and MKBP. Two dimensional gel electrophoresis showed that ischemia increases the hyperphosphorylated form of HSP27. These data suggest that HSP27 and MKBP may be involved in the Z line protection against postischemic reperfusion injury.
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PMID:Translocation of HSP27 and MKBP in ischemic heart. 1053 52

Overexpression studies have shown that the small heat shock proteins (sHSP) protect the myocardium from ischemia-reperfusion (I/R)-induced damage. However, gene deletion studies are necessary to demonstrate whether sHSPs are required for protection. The genes for alphaB-crystallin (alphaBC) and HSPB2, two sHSPs that are expressed in high levels in the heart, are in close proximity to one another; as a result, both genes were disrupted in a recently generated knockout (KO) mouse line. The alphaBC/HSPB2 KO mouse line is currently the only model that features disruption of sHSPs normally expressed in the heart. Accordingly, we examined the cardiac morphology, function, and response to I/R-induced stress in alphaBC-HSPB2 KO mice. Initial gross, light microscopic and echocardiographic characterization showed that the morphological and functional properties of hearts from adult KO mice were indistinguishable from age-matched wild-type (WT) mice. Electron microscopy showed that, compared with WT mouse hearts, KO mouse heart sarcomeres were relatively normal. Isolated perfused KO mouse hearts displayed normal contractility; however, when compared with WT, after I/R, KO mouse hearts exhibited a twofold reduction in contractile recovery, as well as increased necrosis and apoptosis. Additionally, when compared with WT, KO mouse hearts exhibited 43% less reduced glutathione, which is known to protect from I/R-induced damage. Thus, whereas neither alphaBC nor HSPB2 is essential for myocardial development and function under nonstressful conditions, one or both are required for maximal functional recovery and protection from I/R-induced necrosis and apoptosis.
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PMID:Roles for alphaB-crystallin and HSPB2 in protecting the myocardium from ischemia-reperfusion-induced damage in a KO mouse model. 1459 39

The two small heat shock proteins (sHSPs), alphaB-crystallin and HSPB2, have been shown to translocate within a few minutes of cardiac ischemia from the cytosol to myofibrils; and it has been suggested that their chaperone-like properties might protect myofibrillar proteins from unfolding or aggregation during stress conditions. Further evidence of an important role for HSPs in muscle function is provided by the fact that mutations of the alphaB-crystallin gene cause myopathy and cardiomyopathy. In the present study, we subjected isolated papillary muscles of alphaB-crystallin/HSPB2-deficient mice to simulated ischemia and reperfusion. During ischemia in alphaB-crystallin/HSPB2-deficient muscles, the development of contracture started earlier and reached a higher value compared to the wildtype mice. The recovery of contracture of alphaB-crystallin/HSPB2-deficient muscles was also attenuated during the simulated reperfusion period. However, twitch force was not significantly altered at any time of the experiment. This suggests that during ischemic insults, alphaB-crystallin/HSPB2 may not be important for the contraction process itself, but rather serve to maintain muscular elasticity.
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PMID:Ischemia-induced increase of stiffness of alphaB-crystallin/HSPB2-deficient myocardium. 1621 58

Double knockout (DKO) of the small heat shock proteins CRYAB and HSPB2 increases necrosis and apoptosis induced by ischemia/reperfusion (I/R) in vitro, but the mechanisms involved are unknown. We examined [Ca2+]i during metabolic inhibition (MI) changes in [Ca2+]m induced by exposure to elevated [Ca2+]i, and whether mitochondria in isolated DKO ventricular myocytes (VM) are more susceptible than wild type (WT) to induction of the mitochondrial permeability transition (MPT). The rise in [Ca2+]i in DKO myocytes during metabolic inhibition (MI) was less than in WT, and ouabain caused a greater increase in [Ca2+]m in DKO than in WT. These findings suggested that Ca2+ uptake was increased in mitochondria in DKO myocytes. Measurements of Rhod 2 fluorescence during exposure of permeabilized VM to 1000 nM [Ca2+] for 5 min confirmed that DKO myocytes have enhanced mitochondrial Ca2+ uptake, and this difference between DKO and WT myocyte mitochondria was eliminated by inhibition of NO synthesis. MPT was induced more readily by ouabain, PAO, or TMRM in DKO myocytes than in WT. Thus, Ca2+ uptake by mitochondria is increased in DKO VM by a NO-dependent mechanism. This can predispose to the development of MPT, and increased VM injury during I/R. These findings indicate an important role of CRYAB and/or HSPB2 in mitochondrial function.
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PMID:CRYAB and HSPB2 deficiency increases myocyte mitochondrial permeability transition and mitochondrial calcium uptake. 1667 48

CryAB and HSPB2 are small heat shock proteins constitutively expressed in the heart. CryAB protects cytoskeletal organization and intermediate filament assembly; the functions of HSPB2 are unknown. The promoters of CryAB and HSPB2 share regulatory elements, making identifying their separate functions difficult. Here, using a genetic approach, we report distinct roles for these sHSPs, with CryAB protecting mechanical properties and HSPB2 protecting energy reserve. Isolated hearts of wild type mice (WT), mice lacking both sHSPs (DKO), WT mice overexpressing mouse CryAB protein (mCryAB(Tg)), and mice with no HSPB2 made by crossing DKO with mCryAB(Tg) (DKO/mCryAB(Tg)) were stressed with either ischemia/reperfusion or inotropic stimulation. Contractile performance and energetics were measured using 31P NMR spectroscopy. Ischemia/reperfusion caused severe diastolic dysfunction in DKO hearts. Recovery of [ATP] and [PCr] during reperfusion was impaired only in DKO/mCryAB(Tg). During inotropic stimulation, DKO/mCryAB(Tg) showed blunted systolic and diastolic function and revealed massive energy wasting on acute stress: |deltaG(-ATP)| decreased in DKO by 6.4 +/- 0.7 and in DKO/mCryAB(Tg) by 5.5 +/- 0.8 kJ/mol compared with only approximately 3.3 kJ/mol in WT and mCryAB(Tg). Thus, CryAB and HSPB2 proteins play nonredundant roles in the heart, CryAB in structural remodeling and HSPB2 in maintaining energetic balance.
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PMID:Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. 1784 79

The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched ( approximately 5-9 mo) CRYAB/HSPB2 double knockout (DKO) mice were subjected either to 30 min of coronary occlusion and 24 h of reperfusion in situ or preconditioned with a 4-min coronary occlusion/4-min reperfusion x 6, before similar ischemic challenge (ischemic preconditioning). Additionally, WT and DKO mice were subjected to 30 min of global ischemia in isolated hearts ex vivo. All experimental groups were assessed for area at risk and infarct size. Mitochondrial respiration was analyzed in isolated permeabilized cardiac skinned fibers. As a result, DKO mice modestly altered heat shock protein expression. Surprisingly, infarct size in situ was reduced by 35% in hearts of DKO compared with WT mice (38.8 +/- 17.9 vs. 59.8 +/- 10.6% area at risk, P < 0.05). In DKO mice, ischemic preconditioning was additive to its infarct-sparing phenotype. Similarly, infarct size after ischemia and reperfusion ex vivo was decreased and the production of superoxide and creatine kinase release was decreased in DKO compared with WT mice (P < 0.05). In permeabilized fibers, ADP-stimulated respiration rates were modestly reduced and calcium-dependent ATP synthesis was abrogated in DKO compared with WT mice. In conclusion, contrary to expectation, our findings demonstrate that CRYAB and HSPB2 deficiency induces profound adaptations that are related to 1) a reduction in calcium-dependent metabolism/respiration, including ATP production, and 2) decreased superoxide production during reperfusion. We discuss the implications of these disparate results in the context of phenotypic responses reported for CRYAB/HSPB2-deficient mice to different ischemic challenges.
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PMID:CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice. 1787 8