4-Hydroxynonenal induces Cx46 hemichannel inhibition through its carbonylation

Retamal, Mauricio A.; Fiori, Mariana C.; Fernández-Olivares, Ainoa; Linsambarth, Sergio; Peña, Francisca; Quintana, Daisy; Stehberg, Jimmy; Altenberg, Guillermo A.

doi:10.1016/j.bbalip.2020.158705

Cited by 16 publications

(26 citation statements)

References 55 publications

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“…The S-nitrosation of Cx46 (induced with NO donors) increases its hemichannel tail currents and inactivation at positive voltages of 50-60 mV, but does not affect the electrophysiological properties of the Cx46 gap junction channels [48]. The carbonylation of Cx46 (induced with 4-hydroxynonenal) decreases its hemichannel currents and dye uptake [49].…”

Section: Cataracts May Results From Biomineralization In the Lensmentioning

confidence: 99%

“…Alterations of the lens circulation and subsequent biomineralization in the lens may be affected by modifications of the connexins. The lens fiber connexins can undergo several post-translational modifications, including acetylation, phosphorylation, ubiquitination, carbonylation, nitrosation, and cleavage [43][44][45][46][47][48][49]. Their effect on gap junction or hemichannel function is known in some cases.…”

Section: Cataracts May Results From Biomineralization In the Lensmentioning

confidence: 99%

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Connexin Mutants Compromise the Lens Circulation and Cause Cataracts through Biomineralization

Berthoud

Gao

Minogue

et al. 2020

IJMS

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Gap junction-mediated intercellular communication facilitates the circulation of ions, small molecules, and metabolites in the avascular eye lens. Mutants of the lens fiber cell gap junction proteins, connexin46 (Cx46) and connexin50 (Cx50), cause cataracts in people and in mice. Studies in mouse models have begun to elucidate the mechanisms by which these mutants lead to cataracts. The expression of the dominant mutants causes severe decreases in connexin levels, reducing the gap junctional communication between lens fiber cells and compromising the lens circulation. The impairment of the lens circulation results in several changes, including the accumulation of Ca2+ in central lens regions, leading to the formation of precipitates that stain with Alizarin red. The cataract morphology and the distribution of Alizarin red-stained material are similar, suggesting that the cataracts result from biomineralization within the organ. In this review, we suggest that this may be a general process for the formation of cataracts of different etiologies.

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Section: Cataracts May Results From Biomineralization In the Lensmentioning

confidence: 99%

Section: Cataracts May Results From Biomineralization In the Lensmentioning

confidence: 99%

Connexin Mutants Compromise the Lens Circulation and Cause Cataracts through Biomineralization

Berthoud

Gao

Minogue

et al. 2020

IJMS

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“…In particular, the effect of NO on Cx43 hemichannels was associated with an increase in their open probability [87], and in the case of Cx46 hemichannels, with modifications of their electrophysiological properties and changes in their permeability to large molecules [88]. On the other hand, the oxidation of a putative free Cys in one of the extracellular loops seems to induce the closure of the hemichannel by 4-HNE [86]. Interestingly, the Ca 2+ sensor of Cx26 is located at the interface of transmembrane 1 and the extracellular loop 1 [89], and the Cx32 sensor is constituted of several asparagine residues in the extracellular loop 1 [55].…”

Section: Hemichannelsmentioning

confidence: 97%

“…Our group and others have proposed that molecules associated to oxidative stress modulate hemichannel opening [70,[83][84][85][86]. For example, Cx43 hemichannel S-nitrosylation exacerbates hemichannel activity in cerebral ischemia [87] and inflammatory models [62].…”

Section: Hemichannelsmentioning

confidence: 99%

“…For example, Cx43 hemichannel S-nitrosylation exacerbates hemichannel activity in cerebral ischemia [87] and inflammatory models [62]. Despite that the molecular mechanism is unknown, Cx cysteine (Cys) oxidation has been proposed as a mediator in this phenomenon [70,86,88]. In particular, the effect of NO on Cx43 hemichannels was associated with an increase in their open probability [87], and in the case of Cx46 hemichannels, with modifications of their electrophysiological properties and changes in their permeability to large molecules [88].…”

Section: Hemichannelsmentioning

confidence: 99%

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Role of ROS/RNS in Preeclampsia: Are Connexins the Missing Piece?

Rozas-Villanueva

Casanello

Retamal

2020

IJMS

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Preeclampsia is a pregnancy complication that appears after 20 weeks of gestation and is characterized by hypertension and proteinuria, affecting both mother and offspring. The cellular and molecular mechanisms that cause the development of preeclampsia are poorly understood. An important feature of preeclampsia is an increase in oxygen and nitrogen derived free radicals (reactive oxygen species/reactive nitrogen species (ROS/RNS), which seem to be central players setting the development and progression of preeclampsia. Cell-to-cell communication may be disrupted as well. Connexins (Cxs), a family of transmembrane proteins that form hemichannels and gap junction channels (GJCs), are essential in paracrine and autocrine cell communication, allowing the movement of signaling molecules between cells as well as between the cytoplasm and the extracellular media. GJCs and hemichannels are fundamental for communication between endothelial and smooth muscle cells and, therefore, in the control of vascular contraction and relaxation. In systemic vasculature, the activity of GJCs and hemichannels is modulated by ROS and RNS. Cxs participate in the development of the placenta and are expressed in placental vasculature. However, it is unknown whether Cxs are modulated by ROS/RNS in the placenta, or whether this potential modulation contributes to the pathogenesis of preeclampsia. Our review addresses the possible role of Cxs in preeclampsia, and the plausible modulation of Cxs-formed channels by ROS and RNS. We suggest these factors may contribute to the development of preeclampsia.

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