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Voltage-dependent [Ca.sup.2+] channels (VDCCs), which consist of multiple subtypes, regulate vascular tone in developing arterial smooth muscle, including the ductus arteriosus (DA). First, we examined the expression of VDCC subunits in the Wistar rat DA during development. Among [[alpha].sub.1]-subunits, [[alpha].sub.1C] and [[alpha].sub.1G] were the most predominant isoforms. Maternal administration of vitamin A significantly increased [[alpha].sub.1C] and [[alpha].sub.1G]-transcripts. Second, we examined the effect of VDCC subunits on proliferation of DA smooth muscle cells. We found that 1 [micro]M nitrendipine (an L-type [Ca.sup.2+] channel blocker) and kurtoxin (a T-type [Ca.sup.2+] channel blocker) significantly decreased [[sup.3]H]thymidine incorporation and that 3 [micro]M efonidipine (an L- and T-type [Ca.sup.2+] channel blocker) further decreased [[sup.3]H]thymidine incorporation, suggesting that L- and T-type [Ca.sup.2+] channels are involved in smooth muscle cell proliferation in the DA. Third, we found that a novel alternatively spliced variant of the [[alpha].sub.1C]-isoform was highly expressed in the neointimal cushion of the DA, where proliferating and migrating smooth muscle cells are abundant. The basic channel properties of the spliced variant did not differ from those of the conventional [[alpha].sub.1C]-subunit. We conclude that multiple VDCC subunits were identified in the DA, and, in particular, [[alpha].sub.1C] and [[alpha].sub.1G],-subunits were predominant in the DA. A novel spliced variant of the [[alpha].sub.1C]-subunit gene may play a distinct role in neointimal cushion formation in the DA. alternative spliced: development: gene expression: fetal circulation

Abstract Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase family, which activates c-Jun N-terminal kinase and p38 in response to a diverse array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. In the past decade, various regulatory mechanisms of ASK1 have been elucidated, including its oxidative stress-dependent activation. Recently, it has emerged that ASK family proteins play key roles in cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the recent findings on ASK family proteins and their implications in various diseases.

Ferroptosis has recently attracted much interest because of its relevance to human diseases such as cancer and ischemia‐reperfusion injury. We have reported that prolonged severe cold stress induces lipid peroxidation‐dependent ferroptosis, but the upstream mechanism remains unknown. Here, using genome‐wide CRISPR screening, we found that a mitochondrial Ca2+ uptake regulator, mitochondrial calcium uptake 1 (MICU1), is required for generating lipid peroxide and subsequent ferroptosis under cold stress. Furthermore, the gatekeeping activity of MICU1 through mitochondrial calcium uniporter (MCU) is suggested to be indispensable for cold stress‐induced ferroptosis. MICU1 is required for mitochondrial Ca2+ increase, hyperpolarization of the mitochondrial membrane potential (MMP), and subsequent lipid peroxidation under cold stress. Collectively, these findings suggest that the MICU1‐dependent mitochondrial Ca2+ homeostasis‐MMP hyperpolarization axis is involved in cold stress‐induced lipid peroxidation and ferroptosis. SYNOPSIS: This study identifies MICU1 as a key regulator for lipid peroxidation and subsequent ferroptosis under cold stress, suggesting that MICU1 can be a potential target for preventing cell death in organ preservation. Genome‐wide CRISPR screening reveals that MICU1 is required for cold stress‐induced ferroptosis.MICU1 deficiency attenuates lipid peroxidation via suppressing hyperpolarization of the mitochondrial membrane potential and mitochondrial Ca2 + uptake induced by cold stress.Intracellular Ca2 + increase, partly through TRPM8, plays important roles in cold stress‐induced ferroptosis. [ABSTRACT FROM AUTHOR]

VCells are constantly exposed to various types of stress, and disruption of the proper response leads to a variety of diseases. Among them, inflammation and apoptosis are important examples of critical responses and should be tightly regulated, as inappropriate control of these responses is detrimental to the organism. In several disease states, these responses are abnormally regulated, with adverse effects. Apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases that regulate inflammation and apoptosis after a variety of stimuli, such as oxidative stress and endoplasmic reticulum stress. In this review, we summarize recent reports on the ASK family in terms of their involvement in inflammatory diseases, focussing on upstream stimuli that regulate ASK family members. [ABSTRACT FROM AUTHOR]