Human αA- and αB-crystallins prevent UVA-induced apoptosis through regulation of PKCα, RAF/MEK/ERK and AKT signaling pathways

Liu, Jin Ping; Schlosser, R.; Ya, Wei; Dong, Zigang; Feng, Hao; Liu, Long; Huang, Xianwei; Liu, Yan; Li, David Wan Cheng

doi:10.1016/j.exer.2004.06.015

Cited by 120 publications

(120 citation statements)

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“…[3][4][5]9,10,[26][27][28][29][30] Overexpression of aB- crystallin was found to offer protection while silencing rendered cells susceptible to apoptosis from oxidative injury. Signaling mechanisms of cellular protection varied depending on the imposed stress stimuli.…”

Section: Discussionmentioning

confidence: 99%

Antiapoptotic Properties of α-Crystallin–Derived Peptide Chaperones and Characterization of Their Uptake Transporters in Human RPE Cells

Sreekumar

Chothe

Sharma

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Citation: Sreekumar PG, Chothe P, Sharma KK, et al. Antiapoptotic properties of a-crystallin-derived peptide chaperones and characterization of their uptake transporters in human RPE cells. Invest Ophthalmol Vis Sci. 2013;54:278754: -279854: . DOI:10.1167 PURPOSE. The chaperone proteins, a-crystallins, also possess antiapoptotic properties. The purpose of the present study was to investigate whether 19 to 20-mer a-crystallin-derived mini-chaperone peptides (a-crystallin mini-chaperone) are antiapoptotic, and to identify their putative transporters in human fetal RPE (hfRPE) cells. METHODS.Cell death and caspase-3 activation induced by oxidative stress were quantified in early passage hfRPE cells in the presence of 19 to 20-mer aA-or aB-crystallin-derived or scrambled peptides. Cellular uptake of fluorescein-labeled, a-crystallin-derived mini-peptides and recombinant full-length aB-crystallin was determined in confluent hfRPE. The entry mechanism in hfRPE cells for a-crystallin mini-peptides was investigated. The protective role of polycaprolactone (PCL) nanoparticle encapsulated aB-crystallin mini-chaperone peptides from H 2 O 2 -induced cell death was studied.RESULTS. Primary hfRPE cells exposed to oxidative stress and either aA-or aB-crystallin minichaperones remained viable and showed marked inhibition of both cell death and activation of caspase-3. Uptake of full-length aB-crystallin was minimal while a time-dependent uptake of aB-crystallin-derived peptide was observed. The mini-peptides entered the hfRPE cells via the sodium-coupled oligopeptide transporters 1 and 2 (SOPT1, SOPT2). PCL nanoparticles containing aB-crystallin mini-chaperone were also taken up and protected hfRPE from H 2 O 2 -induced cell death at significantly lower concentrations than free aB-crystallin minichaperone peptide.CONCLUSIONS. aA-and aB-crystallin mini-chaperones offer protection to hfRPE cells and inhibit caspase-3 activation. The oligopeptide transporters SOPT1 and SOPT2 mediate the uptake of these peptides in RPE cells. Nanodelivery of aB-crystallin-derived mini-chaperone peptide offers an alternative approach for protection of hfRPE cells from oxidant injury.Keywords: a-crystallin, chaperone peptides, oxidative stress, RPE protection, oligopeptide transporters T he superfamily of small heat shock proteins (sHSPs) has attracted considerable attention in recent years because of its multifunctional cellular properties. The human genome encodes 10 members of the sHSP family, among which aAcrystallin and aB-crystallin are considered important members. 1 Both aA-and aB-crystallins have been studied extensively in the lens for their chaperone and related functions. However, recent studies have identified several novel functions for aA-and aBcrystallins in retina and other tissues in addition to their wellrecognized chaperone function. 2 Both a-crystallins are expressed in RPE cells and in the retina; higher expression of aBcrystallin was found in the RPE while aA-crystallin was found mostly in photoreceptors and astroglial and Mül...

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Section: Discussionmentioning

confidence: 99%

Antiapoptotic Properties of α-Crystallin–Derived Peptide Chaperones and Characterization of Their Uptake Transporters in Human RPE Cells

Sreekumar

Chothe

Sharma

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…For many cell types and stressors, αB-crystallin inhibits apoptosis by preventing the auto proteolytic maturation of caspase-3 (Arrigo et al, 2002;Kamradt et al, 2002). αA-crystallin may also enhance survival by interacting with anti-apoptotic factors Bax and Bcl-xs (Liu et al, 2004). In cultured cells, αB-crystallin was shown to inhibit the activation of ERK signaling pathway and attenuate apoptosis (Li et al, 2005).…”

Section: Cell Survival Is Correlated With Expression Of αA and αB In mentioning

confidence: 99%

The lens epithelium: Focus on the expression and function of the α-crystallin chaperones

Andley

2008

The International Journal of Biochemistry & Cell Biology

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Lens epithelial cells are the parental cells responsible for growth and development of the transparent ocular lens. Many elegant investigations into their biology have focused on the factors that initiate and regulate lens epithelial cell differentiation. Because they serve key transport and cell maintenance functions throughout life, and are the primary source of metabolic activity in the lens, mechanisms to maintain lens epithelial cell integrity and survival are critical for lens transparency. The molecular chaperones α-crystallins are abundant proteins synthesized in the differentiated lens fiber cell cytoplasm. However, their expression in lens epithelial cells has only been appreciated very recently. Besides their important roles in the refractive and light focusing properties of the lens, α-crystallins have been implicated in a number of non-refractive pathways including those involving stress response, apoptosis and cell survival. The most convincing evidence for their importance in the lens epithelium has been shown by studies on the properties of lens epithelial cells from αA and αB-crystallin gene knockout mice. The effective combination of genetics, cell and molecular biology possible with lens epithelial cells is attracting an increasing number of researchers focused on understanding how lens epithelial cells coordinate survival, proliferation and differentiation. Cell facts• Lens epithelial cells are responsible for the growth and development of the entire ocular lens • Lens development is controlled by cell cycle regulators, signaling molecules and growth factors such as FGF • Lens epithelial cells express members of the small heat shock protein family of molecular chaperones, αA and βB-crystallins, the first crystallins to be expressed during lens development • α-Crystallins likely protect lens epithelial cells from environmental stress throughout life, and thus may delay the onset of age-related cataract • Lens epithelial cell proliferation is deregulated in posterior capsule opacification leading to secondary cataract, a complication in up to 50% of cataract surgeries Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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“…Immunoprecipitation-Irradiation of HLECs was conducted as previously described (39). Immunoprecipitation of total proteins from normal or UVA-irradiated cells was conducted as previously described (38,39).…”

Section: Rna Interference To Silence Expression Of Pp-1␣ or Pp-1␤-mentioning

confidence: 99%

“…Immunoprecipitation of total proteins from normal or UVA-irradiated cells was conducted as previously described (38,39).…”

Section: Rna Interference To Silence Expression Of Pp-1␣ or Pp-1␤-mentioning

confidence: 99%

Protein Phosphatase-1 Modulates the Function of Pax-6, a Transcription Factor Controlling Brain and Eye Development

Yan

Liu

Qin

et al. 2007

Journal of Biological Chemistry

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Pax-6 is an evolutionarily conserved transcription factor and acts high up in the regulatory hierarchy controlling eye and brain development in humans, mice, zebrafish, and Drosophila. Previous studies have shown that Pax-6 is a phosphoprotein, and its phosphorylation by ERK, p38, and homeodomain-interacting protein kinase 2 greatly enhances its transactivation activity. However, the protein phosphatases responsible for the dephosphorylation of Pax-6 remain unknown. Here, we present both in vitro and in vivo evidence to show that protein serine/threonine phosphatase-1 is a

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Human αA- and αB-crystallins prevent UVA-induced apoptosis through regulation of PKCα, RAF/MEK/ERK and AKT signaling pathways

Cited by 120 publications

References 65 publications

Antiapoptotic Properties of α-Crystallin–Derived Peptide Chaperones and Characterization of Their Uptake Transporters in Human RPE Cells

Antiapoptotic Properties of α-Crystallin–Derived Peptide Chaperones and Characterization of Their Uptake Transporters in Human RPE Cells

The lens epithelium: Focus on the expression and function of the α-crystallin chaperones

Protein Phosphatase-1 Modulates the Function of Pax-6, a Transcription Factor Controlling Brain and Eye Development

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