Isradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities.

Somatic gain-of-function mutations in the L-type calcium channel CaV1.3 (CACNA1D gene) cause adrenal aldosterone-producing adenomas and micronodules. De novo germline mutations are found in a syndrome of primary aldosteronism, seizures, and neurologic abnormalities (PASNA) as well as in autism spectrum disorder.

Elevated FSP1 protects KRAS-mutated cells from ferroptosis during tumor initiation.

Oncogenic KRAS is the key driver oncogene for several of the most aggressive human cancers. One key feature of oncogenic KRAS expression is an early increase in cellular reactive oxygen species (ROS) which promotes cellular transformation if cells manage to escape cell death, mechanisms of which remain incompletely understood. Here, we identify that expression of oncogenic as compared to WT KRAS in isogenic cellular systems renders cells more resistant to ferroptosis, a recently described type of regulated necrosis.

Extrinsic cell death pathway plasticity: a driver of clonal evolution in cancer?

Human cancers are known to adhere to basic evolutionary principles. During their journey from early transformation to metastatic disease, cancer cell populations have proven to be remarkably adaptive to different forms of intra- and extracellular selective pressure, including nutrient scarcity, oxidative stress, and anti-cancer immunity. Adaption may be achieved via the expansion of clones bearing driver mutations that optimize cellular fitness in response to the specific selective scenario, e.

Dual roles of B lymphocytes in mouse models of diet-induced nonalcoholic fatty liver disease.

Background And Aims: Growing evidence suggests an important role of B cells in the development of NAFLD. However, a detailed functional analysis of B cell subsets in NAFLD pathogenesis is lacking.

Approach And Results: In wild-type mice, 21 weeks of high fat diet (HFD) feeding resulted in NAFLD with massive macrovesicular steatosis, modest hepatic and adipose tissue inflammation, insulin resistance, and incipient fibrosis.

Enhanced Ca signaling, mild primary aldosteronism, and hypertension in a familial hyperaldosteronism mouse model ( ).

Gain-of-function mutations in the gene (encoding the T-type calcium channel Ca3.2) cause autosomal-dominant familial hyperaldosteronism type IV (FH-IV) and early-onset hypertension in humans. We used CRISPR/Cas9 to generate knockin mice as a model of the most common FH-IV mutation, along with corresponding knockout mice ( ).

Retraction notice to "Peptide-induced formation of protein aggregates and amyloid fibrils in human and Guinea pig αA-crystallins under physiological conditions of temperature and pH" [Exp. Eye Res. 179 (2019) 193-205].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

Generation and characterization of a mitotane-resistant adrenocortical cell line.

Mitotane is the only drug approved for the therapy of adrenocortical carcinoma (ACC). Its clinical use is limited by the occurrence of relapse during therapy. To investigate the underlying mechanisms in vitro, we here generated mitotane-resistant cell lines.

Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation.

Gain-of-function mutations in the chloride channel ClC-2 were recently described as a cause of familial hyperaldosteronism type II (FH-II). Here, we report the generation of a mouse model carrying a missense mutation homologous to the most common FH-II-associated CLCN2 mutation. In these Clcn2 mice, adrenal morphology is normal, but Cyp11b2 expression and plasma aldosterone levels are elevated.

Genetic causes of primary aldosteronism.

Primary aldosteronism is characterized by at least partially autonomous production of the adrenal steroid hormone aldosterone and is the most common cause of secondary hypertension. The most frequent subforms are idiopathic hyperaldosteronism and aldosterone-producing adenoma. Rare causes include unilateral hyperplasia, adrenocortical carcinoma and Mendelian forms (familial hyperaldosteronism).

RETRACTED: Peptide-induced formation of protein aggregates and amyloid fibrils in human and guinea pig αA-crystallins under physiological conditions of temperature and pH.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

Genetic mechanisms of human hypertension and their implications for blood pressure physiology.

Hypertension, or elevated blood pressure, constitutes a major public health burden that affects more than 1 billion people worldwide and contributes to ~9 million deaths annually. Hereditary factors are thought to contribute to up to 50% of interindividual blood pressure variability. Blood pressure in the general population approximately shows a normal distribution and is thought to be a polygenic trait.

Intracellular Molecular Differences in Aldosterone- Compared to Cortisol-Secreting Adrenal Cortical Adenomas.

The adrenal cortex is a major site of steroid hormone production. Two hormones are of particular importance: aldosterone, which is produced in the zona glomerulosa in response to volume depletion and hyperkalemia, and cortisol, which is produced in the zona fasciculata in response to stress. In both cases, acute stimulation leads to increased hormone production, and chronic stimulation causes hyperplasia of the respective zone.

CACNA1H(M1549V) Mutant Calcium Channel Causes Autonomous Aldosterone Production in HAC15 Cells and Is Inhibited by Mibefradil.

We recently demonstrated that a recurrent gain-of-function mutation in a T-type calcium channel, CACNA1H(M1549V), causes a novel Mendelian disorder featuring early-onset primary aldosteronism and hypertension. This variant was found independently in five families. CACNA1H(M1549V) leads to impaired channel inactivation and activation at more hyperpolarized potentials, inferred to cause increased calcium entry.