Disease relevance of Cryab

• Moreover, ischemia followed by reperfusion induced a 6.4-fold increase in alpha BC levels in the mitochondrial fractions of TG mouse hearts but no increase in alpha BC levels in any of the other fractions analyzed [1].
• Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain [2].
• The alpha B-crystallin enhancer was active in conjugation with the herpes simplex virus thymidine kinase promoter/human growth hormone reporter gene in transfected rat myocardiocytes [3].
• Together, these data suggest a role for alpha B-crystallin and HSP27 in reactive gliosis and/or in delayed neuronal death proceeded after KA-induced seizure [4].
• The relationship of alpha-crystallin with the family of small heat shock proteins has led to the discovery that the basic subunit alpha B-crystallin can, like other heat shock proteins, protect cells against heat stress [5].

High impact information on Cryab

• Therefore, alpha B-crystallin is not lens-specific and it can accumulate in large amounts in astrocytes in pathological conditions [2].
• In several tissues the amount of hsp25 exceeds that accumulating in NIH 3T3 fibroblasts in response to heat stress. hsp25, like alpha B crystallin, exists in a highly aggregated form in the eye lens [6].
• Targeted disruption of the mouse alpha A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alpha B-crystallin [7].
• We report that in NIH WT-3T3 cells, ceramide induces an enhancement of gene transcription of alpha B-crystallin, a small heat shock protein [8].
• Two-dimensional gel electrophoresis revealed identity between alpha B-crystallin from eye lenses and from heat-treated fibroblasts [9].

Chemical compound and disease context of Cryab

• In rat liver, P23 expression is developmentally regulated and modulated by dietary glucose, and its mRNA is induced by starvation, in the presence of fatty-acids and in 3-MeDAB-induced hepatomas [10].
• The expression of alpha crystallin B chain could be regulated, by medroxy progesterone acetate as well as by oestrogen withdrawal, in human endometrial carcinoma cells (EnCa-101), transplanted to nude mice [11].

Biological context of Cryab

• Orientation-dependent influence of an intergenic enhancer on the promoter activity of the divergently transcribed mouse Shsp/alpha B-crystallin and Mkbp/HspB2 genes [12].
• Furthermore, the patterns of alpha A- and alpha B-crystallin expression in the lens are distinctive: alpha A is upregulated and alpha B is downregulated during prenatal fiber cell differentiation [13].
• It is shown that the single-copy alpha A- and alpha B-crystallin genes are located on different chromosomes [14].
• Here we show that in transgenic mice, the alpha B-crystallin enhancer directs the chloramphenicol acetyltransferase reporter gene driven by the alpha B-crystallin promoter specifically to myocardiocytes of the heart [3].
• The major transcription initiation site of the alpha B crystallin gene in our experimental system was shown by primer extension experiments to be identical with the one used in eye epithelial cells [15].

Anatomical context of Cryab

• 5. During subsequent development of the lens, alpha A crystallin transcripts are most abundant in the fiber cells, and alpha B crystallin mRNA is preferentially expressed in epithelial cells [13].
• In contrast, alpha B-crystallin transcripts are present in retinal pigment epithelium, optic nerve, extraocular muscle, iris, ciliary body, cornea, and several nonocular sites, such as heart and nasal epithelium [13].
• alpha A-crystallin (alpha A) and alpha B-crystallin (alpha B) are among the predominant proteins of the vertebrate eye lens [7].
• In the mouse, significant levels of alpha B-crystallin RNA were detected not only in lens but also in heart, skeletal muscle, kidney, and lung; low and trace levels were detected in brain and spleen, respectively [16].
• Alpha B crystallin accumulation is a specific response to Ha-ras and v-mos oncogene expression in mouse NIH 3T3 fibroblasts [15].

Associations of Cryab with chemical compounds

• The specimens were fixed in paraformaldehyde, histologically processed, and assayed for alpha A- and alpha B-crystallin mRNA expression by in situ hybridization [13].
• Injection of sodium arsenite into mice resulted in increased endogenous alpha B-crystallin expression in the adrenal gland and possibly the liver [17].
• Delayed induction of alpha B-crystallin in activated glia cells of hippocampus in kainic acid-treated mouse brain [4].
• We also demonstrated that the delayed induction of alpha B-crystallin and HSP27 immunoreactivities in the hippocampus of epileptic animals was repressed to the levels seen in control animals with preadministration of the selective nNOS inhibitor 7-nitroindazole (7-NI) [4].
• Morphological characterization of the Alpha A- and Alpha B-crystallin double knockout mouse lens [18].

Regulatory relationships of Cryab

• The small heat shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation [19].
• The expression of heat shock protein hsp 27 was up-regulated whereas alpha B-crystallin was down-regulated in different areas of HSF1 null mouse brain in comparison to control mice [20].

Other interactions of Cryab

• CONCLUSIONS: Transcription of alpha B-crystallin precedes the expression of alpha A-crystallin during murine ocular development [13].
• 0. Mixed polymers can be formed from any combination of alpha A-crystallin, alpha B-crystallin, and HSP25 subunits [21].
• Although there are no complementary human data with which to compare the mice, molecular signs of stress were apparent in the animals, as increased levels of the intermediate filament protein, desmin and the chaperone protein, alpha-B-crystallin, were present in the hearts [22].
• A number of crystallin genes, including that for alpha B-crystallin, are activated by Pax-6, a conserved transcription factor for eye evolution [23].
• We have previously used the herpes simplex virus thymidine kinase promoter fused to the human growth hormone gene to identify an alpha B-crystallin enhancer at positions -427 to -259 that has high activity in muscle and low activity in lens cell lines [24].

Analytical, diagnostic and therapeutic context of Cryab

• Furthermore, the distribution of alpha B-crystallin mRNA in rat organs is consistent with the Western blots [2].
• DNase I footprinting and site-specific mutagenesis experiments showed that alpha BE-1, alpha BE-2, alpha BE-3, MRF, and a novel, heart-specific element called alpha BE-4 are required for alpha B-crystallin enhancer activity in transfected myocardiocytes [3].
• In addition, wild-type alpha B-crystallin promotes xenograft tumor growth and inhibits TRAIL-induced apoptosis in vivo in nude mice, whereas a pseudophosphorylation alpha B-crystallin mutant impaired in its anti-apoptotic function inhibits xenograft tumor growth [25].
• We conclude that IgA MAbs directed to neutralization-sensitive P23 epitopes may have utility in passive immunization against murine C. parvum infection [26].
• Western blots and northern blots showed that H-7 effectively suppressed the accumulation of HSP70 and alpha B-crystallin mRNA as well as the synthesis of their proteins [27].

References