Small Heat Shock Proteins and Vasospasm in Human Umbilical Artery Smooth Muscle1

Brophy, Colleen M.; Beall, Arthur C.; Lamb, Shannon; Dickinson, Mary; Ware, Debra J.

doi:10.1095/biolreprod57.6.1354

Cited by 30 publications

(27 citation statements)

References 16 publications

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“…HSP20 is present in umbilical artery smooth muscle and can be phosphorylated by PKA in vitro using homogenates of umbilical smooth muscle (6). Taken together, these data support a role for phosphorylated HSP20 in mediating cyclic nucleotide-dependent vasorelaxation.…”

supporting

confidence: 56%

The Small Heat Shock-related Protein, HSP20, Is Phosphorylated on Serine 16 during Cyclic Nucleotide-dependent Relaxation

Beall

Bagwell

Woodrum

et al. 1999

Journal of Biological Chemistry

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130

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The small heat shock-related protein 20 (HSP20) is present in four isoforms in bovine carotid artery smooth muscles. Three of the isoforms are phosphorylated and one is not. Increases in the phosphorylation of two isoforms of HSP20 (isoform 3, pI 5.9; and 8, pI 5.7) are associated with cyclic nucleotide-dependent relaxation of bovine carotid artery smooth muscles. Increases in the phosphorylation of another isoform (isoform 4, pI 6.0) are associated with phorbol ester-induced contraction of bovine carotid artery smooth muscles. In this investigation we determined that isoforms 3 and 8 are phosphorylated on Ser 16 of the HSP20 molecule during activation of cAMP-dependent signaling pathways. Phosphorylation state-specific antibodies produced against a peptide containing phosphorylated Ser 16 recognized isoforms 3 and 8 but not isoform 4. In human vascular tissue, only isoform 3 is present. Incubation of transiently permeabilized strips of bovine carotid artery smooth muscle with synthetic peptides in which Ser 16 is phosphorylated, inhibits contractile responses to high extracellular KCl and to serotonin. These data suggest that phosphorylation of HSP20 on Ser 16 modulates cAMP-dependent vasorelaxation.A major phosphorylation event that occurs with cyclic nucleotide-dependent relaxation of vascular smooth muscle is an increase in the phosphorylation of two 20-kDa proteins (isoform 3, pI 5.9; and 8, pI 5.7) (1-3). We recently identified these 20-kDa phosphoproteins as different phosphorylated forms of a small heat shock-related protein, HSP20 1 (4). In addition, HSP20 can be phosphorylated in vitro by both cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) (4). HSP20 is also phosphorylated during endothelialdependent vasorelaxation of isolated segments of bovine carotid artery smooth muscle (5).In a vascular smooth muscle, umbilical artery smooth muscle, that is refractory to cyclic nucleotide-dependent vasorelaxation, there is no significant increase in the phosphorylation of HSP20 in response to activation of PKA or PKG (2). HSP20 is present in umbilical artery smooth muscle and can be phosphorylated by PKA in vitro using homogenates of umbilical smooth muscle (6). Taken together, these data support a role for phosphorylated HSP20 in mediating cyclic nucleotide-dependent vasorelaxation.Histamine and phorbol ester-induced contractions of bovine carotid artery smooth muscle are associated with an increase in the phosphorylation of another 20-kDa protein (isoform 4, pI 6.0) (1). The subsequent activation of cyclic nucleotide-dependent signaling pathways leads to a decrease in the phosphorylation of isoform 4. This 20-kDa protein is immunoreactive with specific polyclonal antibodies raised against HSP20 (4). Thus, increases in the phosphorylation of this isoform of HSP20 are associated with smooth muscle contraction and decreases are associated with activation of cyclic nucleotide-dependent signaling pathways.The purpose of this investigation was to determine the specific site on the HSP20 mo...

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supporting

confidence: 56%

The Small Heat Shock-related Protein, HSP20, Is Phosphorylated on Serine 16 during Cyclic Nucleotide-dependent Relaxation

Beall

Bagwell

Woodrum

et al. 1999

Journal of Biological Chemistry

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130

139

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“…In a muscle that is uniquely refractory to cyclic nucleotidedependent vasorelaxation, human umbilical artery smooth muscle, HSP20 is not phosphorylated (3,4). The macromolecular aggregates of HSP20 from umbilical smooth muscle do not dissociate with activation of cyclic nucleotide-dependent signaling pathways.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, endothelial-dependent vasodilation of isolated segments of bovine carotid arteries is also associated with increases in the phosphorylation of HSP20 (2). However, HSP20 is not phosphorylated in a muscle that is uniquely refractory to cyclic nucleotide-dependent relaxation, human umbilical artery smooth muscle (3,4). These data suggest that increases in the phosphorylation of HSP20 may mediate cellular signaling processes that lead to vasorelaxation.…”

mentioning

confidence: 91%

Phosphorylation of the Small Heat Shock-related Protein, HSP20, in Vascular Smooth Muscles Is Associated with Changes in the Macromolecular Associations of HSP20

Brophy

Dickinson

Woodrum

1999

Journal of Biological Chemistry

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Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20. We hypothesized that phosphorylation of HSP20 in vascular smooth muscles is associated with alterations in the macromolecular associations of HSP20. Treatment of bovine carotid artery smooth muscles with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and the adenylate cyclase activator, forskolin, led to increases in the phosphorylation of HSP20 and dissociation of macromolecular aggregates of HSP20. However, 3-isobutyl-1-methylxanthine and forskolin treatment of a muscle that is uniquely refractory to cyclic nucleotide-dependent vasorelaxation, human umbilical artery smooth muscle, did not result in increases in the phosphorylation of HSP20 or to dissociation of macromolecular aggregates. HSP20 can be phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase (PKA) in both carotid and umbilical arteries and this phosphorylation of HSP20 is associated with dissociation of macromolecular aggregates of HSP20. Activation of cyclic nucleotide-dependent signaling pathways does not lead to changes in the macromolecular associations of another small heat shock protein, HSP27. Interestingly, the myosin light chains (MLC 20 ) are in similar fractions as the HSP20, and phosphorylation of HSP20 is associated with changes in the macromolecular associations of MLC 20 . These data suggest that increases in the phosphorylation of HSP20 are associated with changes in the macromolecular associations of HSP20. HSP20 may regulate vasorelaxation through a direct interaction with specific contractile regulatory proteins.Agonist pre-contracted bovine carotid artery smooth muscle relaxes with the addition of the guanylyl cyclase activator, sodium nitroprusside, or the adenylyl cyclase activator, forskolin. This relaxation is associated with increases in the phosphorylation of the small heat shock-related protein, HSP20 1 (1). In addition, endothelial-dependent vasodilation of isolated segments of bovine carotid arteries is also associated with increases in the phosphorylation of HSP20 (2). However, HSP20 is not phosphorylated in a muscle that is uniquely refractory to cyclic nucleotide-dependent relaxation, human umbilical artery smooth muscle (3,4). These data suggest that increases in the phosphorylation of HSP20 may mediate cellular signaling processes that lead to vasorelaxation. HSP20 was initially identified as a by-product of the purification of another small heat shock protein, HSP27 (5). HSP27 has been shown to modulate actin filament dynamics in cultured cells (7-9). Increases in the phosphorylation of HSP27 have been associated with vascular smooth muscle contraction (10 -12). HSP20 has been shown to associate in macromolecular aggregates with HSP27, in extracts from heart, diaphragm, and soleus muscle cells (5). Both HSP20 and HSP27 dissociate from the aggregated form in response to heat stress (5, 6). HSP20 and HSP27 are predominant proteins in ...

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“…PKG and PKA phosphorylate specific substrate proteins including HSPB6. HSPB6 phosphorylation on serine 16 has been demonstrated to mediate smooth muscle relaxation (Beall et al , 1999Brophy et al 1997;Jerius et al 1999;Woodrum et al 1999;Rembold et al 2000;Tessier et al 2004a, b;Flynn et al 2007). …”

Section: Hspb6 and Smooth Musclementioning

confidence: 99%

The small heat shock protein, HSPB6, in muscle function and disease

Dreiza

Komalavilas

Furnish

et al. 2010

Cell Stress and Chaperones

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The small heat shock protein, HSPB6, is a 17-kDa protein that belongs to the small heat shock protein family. HSPB6 was identified in the mid-1990s when it was recognized as a by-product of the purification of HSPB1 and HSPB5. HSPB6 is highly and constitutively expressed in smooth, cardiac, and skeletal muscle and plays a role in muscle function. This review will focus on the physiologic and biochemical properties of HSPB6 in smooth, cardiac, and skeletal muscle; the putative mechanisms of action; and therapeutic implications.

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Small Heat Shock Proteins and Vasospasm in Human Umbilical Artery Smooth Muscle1

Cited by 30 publications

References 16 publications

The Small Heat Shock-related Protein, HSP20, Is Phosphorylated on Serine 16 during Cyclic Nucleotide-dependent Relaxation

The Small Heat Shock-related Protein, HSP20, Is Phosphorylated on Serine 16 during Cyclic Nucleotide-dependent Relaxation

Phosphorylation of the Small Heat Shock-related Protein, HSP20, in Vascular Smooth Muscles Is Associated with Changes in the Macromolecular Associations of HSP20

The small heat shock protein, HSPB6, in muscle function and disease

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