Alpha B-crystallin expression in mouse NIH 3T3 fibroblasts: glucocorticoid responsiveness and involvement in thermal protection.

Abstract

ocB-crystallin, a major soluble protein of vertebrate eye lenses, is a small heat shock protein which transiently accumulates in response to heat shock and other kinds of stress in mouse NIH 3T3 fibroblasts. Ectopic expression of an aeB-crystallin cDNA clone renders NIH 3T3 cells thermoresistant. avB-crystallin accumulates in response to the synthetic glucocorticoid hormone dexamethasone. Dexamethasone-treated NIH 3T3 cells become thermoresistant to the same extent as they accumulate cvB-crystallin. A cell clone in which ciB-crystallin is superinduced upon heat shock acquires augmented thermotolerance. Expression of the ras oncogene causes a rapid but transient accumulation of cfB-crystallin within 1 day. Later, sustained ras oncogene expression suppresses the dexamethasone-mediated aB-crystallin accumulation. Thus, oncogenic transformation triggered by the ras oncogene interferes with hormone-mediated accumulation of oaB-crystallin and concomitant acquisition of thermoresistance. Other known heat shock proteins do not accumulate in response to ectopic csB-crystallin expression or to dexamethasone treatment. These results indicate that aB-crystallin can protect NIH 3T3 fibroblasts from thermal shock.Studies on oncogene-induced alterations in cellular gene expression and their association with the transformation phenotype are essential for understanding the mechanisms by which oncogenes mediate the malignant phenotype (for a review, see reference 3). In an attempt to define specific cellular responses toward accumulation of oncoproteins, we have previously studied the effects of the ras and mos oncoproteins on cellular gene expression in mouse NIH 3T3 fibroblasts (34). We found that high amounts of aB-crystallin rapidly accumulate in NIH 3T3 cells in response to the expression of the c-Ha-ras and v-mos oncogenes controlled by the glucocorticoid-inducible promoter of mouse mammary tumor virus (MMTV) (32).aB-crystallin is one of the major soluble proteins of vertebrate eye lenses (for reviews, see references 51, 52, and 67). The protein shares 60% amino acid sequence homology with oA-crystallin (62). atB-crystallin is also expressed in nonocular tissues such as heart muscle, skeletal muscle, kidney, lung, brain, spermatocyte, and placenta (5, 8, 12, 23-25, 31, 40). Moreover, evidence has been accumulating that elevated levels of aB-crystallin are associated with various pathological conditions in the brain and other tissues (13,24,26,27,43,44,48). The ot-crystallins share amino acid sequence similarity with small heat shock proteins (hsps) of diverse organisms, including mycobacteria, fruit flies, plants, and mammals (for reviews, see references 39, 51, 52, 65, 66, and 67). The homology between mouse aB-crystallin (32) and hsp25 (unpublished data; 17) reaches approximately 40%. These observations suggest a possible functional relationship between a-crystallins and small hsps (11). Recently we have shown that oxB-crystallin is indeed a bona fide small hsp (33). The characteristic features shared by aB-crystallin a...

Human αA- and αB-crystallins bind to Bax and Bcl-XS to sequester their translocation during staurosporine-induced apoptosis

“…[39][40][41][42][43][44][45][46][62][63][64][65][66][67][68][69][70][71][72][73][74] One of the most important functions is the ability to protect cell from induced apoptosis. 39-46 a-Crystallin and Hsp27 are closely related family members and protect cells from apoptosis induced by a large numbers of stress factors.…”

“…62 Later, a-crystallins are found to act as molecular chaperones [63][64][65][66][67] and also display autokinase activity. 68,69 As antiapoptotic regulators, acrystallins are initially shown to protect cells from thermal, 70 osmotic 71 and oxidative insult. 72 More recently, a-crystallins have been shown to prevent induced apoptosis by various factors including staurosporine, [39][40]43 TNF, 39,43 UVA irradiation, 43 okadaic acid 44 and hydrogen peroxide.…”

α-Crystallins, versatile stress-proteins

“…Evidence for this is the strong correlation between increased expression of aB-crystallin and the enhanced resistance of the cell to stress [9,62,87]. Also aA-crystallin, which is not stress inducible, con fers cellular thermoresistance [63].…”

“…a-Crystallins and small hsps arc not only evolutionarily related but they also behave very similarly in many respects. They actu ally can form mixed complexes in tissues were both proteins are expressed [6 , 7], a-Crystallins, like oth er small hsps, have chaperone-like properties in that they can prevent stress-induced aggregation of pro teins [8], Furthermore, mammalian aB-crystallin is stress-inducible, and the presence of a-crystallins in cultured cells leads to an enhanced survival of these cells after a period of stress [9]. aB-Crystallin is also implicated in the pathogenesis of various degenerative diseases.…”

Redistribution of GFAP and αB-crystallin after thermal stress in C6 glioma cell line

“…aB-crystallin is also found expressed constitutively in non-lenticular tissue such as skeletal or cardiac muscle and kidney [16][17][18]. This small HSP is inducible in many different cell types by several kinds of physiological stress [19,20], and acts as a molecular chaperone by preventing heat-induced protein aggregation in vitro [21]. It was also reported that aB-crystallin can interact with intermediate filament in muscle, the lens, and astrocytes [22][23][24][25], and inhibits the intermediate filament protein assembly in vitro [23,25].…”