Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs

He, Wencheng; Huang, Lei; Luo, Hua; Yang, Zhiping; An, Yi; Zhang, Weixing

doi:10.3855/jidc.12341

Cited by 13 publications

(17 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypothesis is supported by the fact that the administration of a calcium channel blocker results in a better prognosis and a reduction in mortality rates of septic patients [35]. These data corroborate with experimental findings; the administration of verapamil in septic animals resulted in a reduction of mortality, attenuation of cardiac lesions, reduction of intracellular calcium concentration, and attenuation of hypocalcemia [31,32,36]. The data from the present study also supports this hypothesis, as septic animals treated with verapamil survived longer than septic animals without treatment.…”

Section: Discussionsupporting

confidence: 69%

“…A previous study from our research group showed an increase in [Ca 2+ ] i in cultured neonatal cardiomyocytes treated with septic animal serum [31]. Calcium overload by CLP has also been demonstrated in the heart, brain, liver, and spleen cells of septic rats [32]. The hypotheses for this increase in [Ca 2+ ] i involve failures in the channels that regulate the entry of Ca 2+ , microruptures in the plasma ) groups were measured 6, 12, and 24 hours after CLP surgery and expressed in arbitrary units (AUs).…”

Section: Discussionmentioning

confidence: 76%

“…However, one hypocalcemia hypothesis suggests that sepsis-induced failures in calcium channels cause an increased influx of Ca 2+ into cells [32]. This hypothesis is supported by the fact that the administration of a calcium channel blocker results in a better prognosis and a reduction in mortality rates of septic patients [35].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of Verapamil, an L‐Type Calcium Channel Inhibitor, on Caveolin‐3 Expression in Septic Mouse Hearts

Rattis

Freitas

Oliveira

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Sepsis-induced myocardial dysfunction considerably increases mortality risk in patients with sepsis. Previous studies from our group have shown that sepsis alters the expression of structural proteins in cardiac cells, resulting in cardiomyocyte degeneration and impaired communication between cardiac cells. Caveolin-3 (CAV3) is a structural protein present in caveolae, located in the membrane of cardiac muscle cells, which regulates physiological processes such as calcium homeostasis. In sepsis, there is a disruption of calcium homeostasis, which increases the concentration of intracellular calcium, which can lead to the activation of potent cellular enzymes/proteases which cause severe cellular injury and death. The purpose of the present study was to test the hypotheses that sepsis induces CAV3 overexpression in the heart, and the regulation of L-type calcium channels directly relates to the regulation of CAV3 expression. Severe sepsis increases the expression of CAV3 in the heart, as immunostaining in our study showed CAV3 presence in the cardiomyocyte membrane and cytoplasm, in comparison with our control groups (without sepsis) that showed CAV3 presence predominantly in the plasma membrane. The administration of verapamil, an L-type calcium channel inhibitor, resulted in a decrease in mortality rates of septic mice. This effect was accompanied by a reduction in the expression of CAV3 and attenuation of cardiac lesions in septic mice treated with verapamil. Our results indicate that CAV3 has a vital role in cardiac dysfunction development in sepsis and that the regulation of L-type calcium channels may be related to its expression.

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 76%

See 1 more Smart Citation

Effect of Verapamil, an L‐Type Calcium Channel Inhibitor, on Caveolin‐3 Expression in Septic Mouse Hearts

Rattis

Freitas

Oliveira

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Indeed, iron binding by specific chelators was found to be effective in a number of cases of sepsis, and, moreover, iron chelation specifically altered the microbiota profile [ 55 , 56 ]. The same relates to disorders of calcium homeostasis in infections and sepsis, which are manifested in a decrease in Ca 2+ concentration in the blood and its overload in cytosol and mitochondria [ 33 , 34 , 35 ]. As follows from our data, each of these factors enhances the effect of microbial metabolites on mitochondrial membrane permeability almost tenfold, reducing their active concentration.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in Ca 2+ levels in bodily fluids and subcellular compartments were found in different sepsis models. They were manifested in a decrease in the blood Ca 2+ concentration and calcium overload in cytosol, endoplasmic reticulum and mitochondria [ 32 , 33 , 34 ]. Moreover, it has been shown that the inhibition of mitochondrial permeability transition by cyclosporine A prevented sepsis-induced myocardial dysfunction and mortality [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of Microbial Metabolites on the Nonspecific Permeability of Mitochondrial Membranes under Conditions of Acidosis and Loading with Calcium and Iron Ions

2021

View full text Add to dashboard Cite

Mitochondrial dysfunction is currently considered one of the main causes of multiple organ failure in chronic inflammation and sepsis. The participation of microbial metabolites in disorders of bioenergetic processes in mitochondria has been revealed, but their influence on the mitochondrial membrane permeability has not yet been studied. We tested the influence of various groups of microbial metabolites, including indolic and phenolic acids, trimethylamine-N-oxide (TMAO) and acetyl phosphate (AcP), on the nonspecific permeability of mitochondrial membranes under conditions of acidosis, imbalance of calcium ions and excess free iron, which are inherent in sepsis. Changes in the parameters of the calcium-induced opening of the mitochondrial permeability transition pore (MPTP) and iron-activated swelling of rat liver mitochondria were evaluated. The most active metabolites were indole-3-carboxylic acid (ICA) and benzoic acid (BA), which activated MPTP opening and swelling under all conditions. AcP showed the opposite effect on the induction of MPTP opening, increasing the threshold concentration of calcium by 1.5 times, while TMAO activated swelling only under acidification. All the redox-dependent effects of metabolites were suppressed by the lipid radical scavenger butyl-hydroxytoluene (BHT), which indicates the participation of these microbial metabolites in the activation of membrane lipid peroxidation. Thus, microbial metabolites can directly affect the nonspecific permeability of mitochondrial membranes, if conditions of acidosis, an imbalance of calcium ions and an excess of free iron are created in the pathological state.

show abstract

TLR4 inhibitor alleviates sepsis-induced organ failure by inhibiting platelet mtROS production, autophagy, and GPIIb/IIIa expression

Liu

Guo

2022

J Bioenerg Biomembr

View full text Add to dashboard Cite

Thrombocytopenia and impaired platelet aggregation are associated with sepsis-induced organ failure.Many studies have shown that mitochondrial ROS, autophagy is related to organ injury in sepsis. However, the relationship between them is unknown. Here, we explored whether Toll Like Receptor 4 inhibitor alleviates sepsis organ failure by inhibiting platelet mitochondrial ROS production, autophagy, and GPIIb/IIIa expression. We found Toll Like Receptor 4 inhibitor TAK242 alleviated LPS-induced acute kidney and lung injury and decrease platelet activation in a mouse model of sepsis mice. In vitro study, inhibiting Toll Like Receptor 4 reduced inward ow of Ca 2+ and decreased endogenous mitochondrial ROS production in platelets treated with LPS, and TAK242 inhibited autophagy and NOX expression in LPS treated platelets. Thus, we supposed that Toll Like Receptor 4 inhibitor effectively alleviate lung and kidney injury in a mouse model of sepsis induced by LPS and its effects are related to the inhibition of mouse platelets GPIIb/IIIa, and also can reduce LPS-induced mitochondrial ROS generation related to Ca 2+ in ux, thus reducing platelet activation. LPS can induce platelet autophagy by generating mitochondrial ROS, which may be the pathophysiological mechanism of organ injury in sepsis.

show abstract

Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs

Cited by 13 publications

References 40 publications

Effect of Verapamil, an L‐Type Calcium Channel Inhibitor, on Caveolin‐3 Expression in Septic Mouse Hearts

Effect of Verapamil, an L‐Type Calcium Channel Inhibitor, on Caveolin‐3 Expression in Septic Mouse Hearts

Influence of Microbial Metabolites on the Nonspecific Permeability of Mitochondrial Membranes under Conditions of Acidosis and Loading with Calcium and Iron Ions

TLR4 inhibitor alleviates sepsis-induced organ failure by inhibiting platelet mtROS production, autophagy, and GPIIb/IIIa expression

Contact Info

Product

Resources

About